Mutation, Repair, and Mechanism of Cancer Development
Double and neoplasia or tumors are the growth of new cells that proliferate
uncontrollabilities without having clear and irregular functions. The term
tumor which means different swelling with other shirts such as abscesses,
chronic inflammation, parasitic nodules. The process of the occurrence of
tumors involves many factors, so the cause of the occurrence of tumors is
divided into intrinsic factors: offspring, age, pigment, sex and immunity and
extrinsic factors: chemicals, hormones, chronic irritation, ultraviolet, radiation,
parasites, viruses. In the case of multiple growing, it has a picture of the lesion
as follows:
a. Macroscopic overview There are several factors that affect the location,
type / properties, blood supply and length of time tumors but cannot be
ascertained the size, shape, color and consistency. The size of the tumor
ranges from 1-2 mm to several centimeters, the tumor form varies
between round, oval, ellipse, or multi lobe. The color of the tumor can be
gray, yellow, red, brown or black. The consistency of the tumor depends
on the location of the network or the affected organs, for example in the
tumor bone concentrating hard, while the connective tissue has soft or
elastic consistency.
b. The microscopic description shows tumor cells are no different from
other cells. Malignant tumor cell differences are more dominated by
young or embryonic cells (anaplasia), while benign of tumor cells are
dominated by adult cells.
Tumor cells can spread other pecipation in the animal body, namely by means
of infiltration, metastasis and implantation. The process of spreading tumor
cells by means of infiltration is the most common way of malignant cells with
loose ties, parenchymes and cell interstitial. The spread can also through blood
vessels and lymph so that malignant cells can grow in the area of blood vessels.
The spread of tumor cells by means of metastasis through blood vessels and
lymphs with embolic cells (metastases). And the spread of tumor cells by
transplanting more dominant direct contact tumor cells on the surface of the
mucous layer or serous.
The classification of tumors based on the ferocity of cell ferocity can be non-
malignant (benigna) and malignant (malignant). Characteristics of Benigna
Tumor cells include a single, round, elliptical, stemming, slow, slow growing,
rarely no necrosis, easy to take, not toxic, not metastatic, does not grow
anymore and usually does not cause death. While in malignant tumor cells are
multiple, irregular, not capsuled, growing fast, often necrosis, difficult to lift,
toxic
For animals, infiltratives, invasive, metastatic, tend to grow again and cause
death.
Classification of tumors based on the origin of the cell, namely:
1. Epithelial tumor cells: tumor cells from epithel squamus or glandular,
among others who are benigned: papiloma, adenoma. Which is malignant:
carcinoma.
2. Non epithelia tumor cells: tumor cells originating from connective tissue,
for example benigna: fibroma, osteoma, chondroma, malignant tumor
cells fibrosarcoma, osteosarcoma, chondrosarcoma (Network / Organ
name + Sarcoma).
Tumor cells are very detrimental to animal bodies. Effects or severity of tumor
cells to the network or organs depend on the location of tumor cells, the tissue
of the origin of tumor cells and benign or maligned tumor cell properties. The
process of tumor cell growth will cause interference in the body in the form of:
a. Pressing the cell / network around it: Tumor cells are crowded that
presses the surrounding tissue.
b. Organ lumen obstruction: the growth of tumor cells that clog in ingesta
flow, secretion and organ excretion.
c. Damage of blood vessels and lymph: Tumor cells that enter the wall
endothelia cause damage to blood vessels / lymph.
d. Damage to the nervous system: due to tumor cells that suppress the tissue
and blood vessels.
e. Secondary germ infection.
f. Anemia: When the tumor cells damage blood vessels, resulting in the
release of blood into the network.
g. Hormone production disorders.
h. Death: Tumor cells that attack vital organs cause failure of body system
functions.
Carcinogens
Carcinogenesis is one of the slowest biological processes known. The
similarities possessed by all neoplastic cells are disruption to their DNA. This
disorder causes excessive cell proliferation. Each cancer case is usually the
result of a series of events - environment, genetics, immunology, and other
factors. The main cancer-causing agent (carcinogen) is included in three main
groups: chemical, virus, and physical. The development, however, also shows
that tumors really consist of heterogeneous cell populations, because individual
tumor cells experience additional mutations after initiation that choose the cell
clone. Most neoplasia comes from monoclonal, which means that all cells in
certain neoplasia come from one cell that is transformed in terms of
transforming mutations. Carcinogenesis is best seen as a multi-step process that
involves the concept of initiation, promotion, and progression. Following are
the formation stages:
1. Initiations that change the genome. Chemical, physical or biological
agents that cause permanent damage (mutations) to DNA. In the classic
model of chemical carcinogenesis, this step is considered to be inherited
and cannot be changed. In essence, the effect is genotoxicity (damage to
cell genetic machines).
2. Promotions - events that cause cell proliferation to change. Cell
proliferation is a typical promoter effect. The neoplastic changes may or
may not be expressed at this time. Hormones such as estrogen and certain
proliferation factors can act as promoters
3. Progressions - imply that cells that begin experience additional mutations,
through a series of cell division, and further transformation, ultimately
result in the development of neoplasia. Neoplasia is a cell population that
comes from one mutating cell. They are clonal but heterogeneous.
Changes in cell characteristics when the populastic population develops are
referred to as the development of tumors. Developments can be seen as a series
of steps where mutated cells evolved into neoplasia. Think of development as a
tumor cell that changes from bad getting worse. Genelled, the development of
tumors implies that neoplastic cells emerge from many genetic defects and
damaged DNA repairs may support this process. Most neoplasia comes from
monoclonal, which means that all cells in certain neoplasia come from one cell
that is transformed in terms of transforming mutations.
The development, however, also shows that tumors really consist of
heterogeneous cell populations, because individual tumor cells experience
additional mutations after initiation that choose responsive cell clones that vary
to certain hormones, more aggressive (can invade and Acting, has a greater
survivality (faster growth rate; can avoid immune responses). Only in mice
groups where promoters are applied at the right time after initiation,
progressions become a production of tumors. And it is eternal (continuing to
replicate without limits Time. There are some neoplasia that can develop from
hyperplasia into neoplasia; However, not all neoplasia do this. Examples of
developing neoplasia from hyperplasia through dysplasia into neoplasia are
squamous epithelial neoplasia (eg papiloma squamous, squamous cell
carcinoma.
Chemical carcinogens include human and natural substances. Most trigger
chemicals are mutagen - chemicals that cause mutations. In the classic model of
chemical carcinogenesis, initiation is considered to be inherited and cannot be
changed. A large number of mutagens are involved in the causes of cancer in
humans and laboratory animals. The results of malignant transformation when
chemical mutagen interacts with cell fixer genes (proto-oncogen, cancer
suppressing genes, and genes that regulate apoptosis). The properties of
carcinogens are mostly chemical carcinogens are not active in their home state.
These chemicals must experience metabolic activation into a very reactive (and
electrophile) form and electrophiles bind to DNA, RNA, and cell protein causing
mutations.
Chemical Carcinogens Work Directly - small groups of carcinogens are reactive
in their original state. This materium does not require metabolic conversion to
carcinogenic. Chemical carcinogens that work indirectly - most chemical
carcinogens are included in this group. This chemical requires metabolic
conversion to its active situation. Metabolic activation occurs in the cell
endoplasmic reticulum by the Cytochrome P-450 oxygenase system. Organs with
a large number of enzymes that metabolize poisons, such as liver, are often
targeted by chemical carcinogens. Also, the bladder is often influenced by
carcinogens whose metabolites are excreted in urine
Physical carcinogens (radiation-ultraviolet and ionizing)
Ultraviolet (sunlight) is a complete carcinogen but repeat exposure is needed.
UV rays damage DNA and also tend to suppress the immune system. Squamous
cell carcinoma, basalt cell tumors, and malignant melanoma are general tumors
associated with exposure to sunlight repeatedly. Ocular squamous cell
carcinoma on the beef Hereford (called eye cancer) and squamous cell
carcinoma on the white cat's ear is a classic example of cancer due to UV light.
Mental radiation includes exposure to our natural environment (cosmic rays
and terrestrial radiation) and medical and industrial sources (X-rays and gamma
rays). Unlike UV rays, single exposure to ionizing radiation is enough to cause
cancer. Teer radiation causes damage to DNA which causes cell death and
increased mutations. Chronic inflammation can cause an enzyme elaboration
such as Siklo-oxygenase (COX 2) which can increase growth factors, and
stimulate cell proliferation. In the right environment, this can cause hyperplasia
and metaplasia, then eventually become a dysplasia and neoplasia. Helicobacter
pylori has been associated with stomach adenocarcinoma in humans. In
animals, Spirocerca Lupi, parasitesophagus has been suspected in the case of
esophageal fibrosaroma and osteosarcoma.
Disorders in genes that regulate cell growth, differentiation and repair of DNA
become a central neoplastic transformation. Proto-oncogen (P-ONC) is a normal
cellular genes that encourage growth and differentiation of normal cells. More
than 100 proto onkogents has been characterized. ONKOGEN - is a cellular gene
mutated that interferes with cell growth and causes cancer.
Oncogenes are initially isolated from the RNA retrovirus forming tumor (V-
ONCS). Knowledge of the subsequent virus oncogenes leads to the discovery of
the order of homologous genes in normal cells. Proto-oncogen is a gene that is
usually associated with cell growth. They produce growth factors, signal
transduction factors, growth factor receptors and proteins that activate
transcription RNA. When this gene mutates, there is excessive production or
abnormal production of this gene product which results in abnormal cell
growth and neoplasia. Mutated genes called oncogen.
ONKOGEN is a mutated proto-oncogen. ONKOGEN can cause neoplasia
development through three mechanisms: with mutations - the mutation of
abnormal protein products, amplification-causes the advantages of protein
products and promotion of abnormal-oncogen genes driven (controlled) by
promoter abnormal (promoter can come from the host or virus derivative).
Cellular oncogen (C-ONCS) - is the proto- oncogen that has been changed by its
structure or function so that it behaves like a cancer-causing gene, oncogen.
Cellular oncogenes are named so to distinguish from viral oncogenes. Virus
oncogen (V-ONCS) - is a sequence of genes carried by a virus that can induce cell
transformation. Genes that regulate these apoptosis-genes controlled
programmed cell deaths. The BCL-2 gene family inhibits (BCL-2) or promoting
(Bax) apoptosis. Many cancer cells have increased the amount of BCL-2 protein.
Oncogenous products (onkoprotein) are basically the version that is changed
from its normal product, onkoprotein is different from normal regulatory
proteins because the production is not regulated.
Onkoprotein basically takes control of signal transduction and cell growth.
Onkoprotein serves to provide growth benefits in mutating cells. Keep in mind,
however, that most neoplasia types resultden from many mutations, and that
carcinogenesis is a multi-step process, and changes in genotypes and
phenotypes are an integral part of the development of tumors. Genetic damage
(or mutations) can be initiated by environmental agents such as chemicals,
viruses, radiation, or may be inherited in germinal cells. Anti-oncogenic genes
or tumor suppressors are genes that inhibit normal cell proliferation and thus
offset the proto-oncogen effect. If this gene mutates, the inhibition of cell
proliferation is removed so that neoplasia occur. An anti-oncogen example is
the P53 gene. This gene encodes the protein that sends cells with damaged DNA
into apoptosis (suicide cells). If this gene mutates, the cell is not told to die,
continue to replicate and cancer.
Telomer is a recurrent DNA sequence located at the end of the chromosome.
Germinal cells, stem cells, and the Selembrionics express enzymes called
telomerase that allows telomere to be replicated and this contributes to the cell's
ability to continue. Adult cells gradually lose the ability to express telomerase
and the results of telomers no longer replicate but it becomes shorter. When
Telomer is growing shorter, finally it reaches the limit of the replication
capacity and dies. This is considered the main cause of aging. Many
selneoplastics get back their ability to produce telomerase, so that cells get the
ability to replicate without limits. Therefore, to review, the neoplasia results of
some genetic and epigenetic changes (due to factors other than DNA changes).
These changes can be caused by ionizing radiation, various chemical
carcinogens, oncogens, tumor suppressant genes, viruses, and telomerase
activities. The cumulative effect of all these changes in a long period of time can
result in carcinogenesis.
Neoplasia
Neoplasia is named based on the network that first develops. For example,
malignant neoplasia epithelials on the surface of the skin that spread to the
heart remains squamous cell carcinoma even though in the liver. Similarly,
malignant neoplasia the heart that spreads to the skin remains a wild
adenocarcinoma even though it is on the skin.
The term adenoma is applied to benign neoplasia from the epithelium that
forms the pattern of gland or asilar and tumors that come from the gland that
forms solid cell masses. Adenoma containing cavities (cysts) are called
cistadenomas. The benign papillary adenoma that appears from the surface is
called polyp or papilloma. The neoplastic part is just an epithelium cover; The
core of the connective tissue only adds the severity. Polyps appear as soft fleshy
growth stand out from the surface of the secretory epithelium.
Malignant epithelial neoplasia is called carcinoma. which has a microscopic
gland growth pattern called adenocarcinoma. They can have a pattern of growth
similar to those that are seen in adenoma but looks much heavier. Carcinoma in
situ is epithelial cell neoplasia that meets all pathological criteria for
malignancy except that it does not invade the structure of supporting organs
where it appears. In situ "is Latin, and literally translated into English as" in
place.
The technical definition of in situ is the presence of malignant cells in the cell
group where they come from. There is no basic network penetration and no
stroma invasion. Generally, neoplasia begins on epithelial cells of organs
splitting quickly and growing from outside the organ. Diagnosis in situ can only
be done microscopically. Must identify the base membrane and determine that
the membrane has not been penetrated, if the basement membrane has been
invested, the case is no longer in situ and at least localized. Organs and
networks that do not have an epithelial layer cannot be shown in situ, because
they do not have a basic membrane. Therefore, there cannot be a diagnosis in
situ in connective tissue tumors because the connective tissue does not have a
basic membrane.
Tame neoplasia ties (mesencehmal) are only named by adding OMA suffix to the
type of proliferation. The ferocious tumor tissue tie is named by adding the
suffix, sarcoma: hence fibrosarcoma, liposarcoma, hemangiosarcoma,
osteosarcoma, and so on.
Neoplasia with differentiated well consists of cells that are very similar to the
origin network (see the diagram on the top left below). Neoplasia that
differentiated badly only shows a resemblance to a glance with its original
network. This is called Anaplasia. Anaplastic tumors come from cells that do not
differentiate and thus their original network cannot be identified only with
morphological characteristics. They show characteristics such as pleomorphism
of anisocytosis, and anisocaryaososis (various sizes and shapes of cells and
nucleus), abnormal mitotic numbers, increased core and basophylia cytoplasm,
increased core ratio to cytoplasms, a lot nucleolus, and multinucleation. These
criteria are called "malignancy criteria.
Anaplasia is only seen in malignant neoplasia; It is not visible to benign
neoplasia. Anaplasia is in degree; that
Representing the spectrum of changes and may be severe or mild, therefore, it
is pathologically not only observing the absence or existence of anaplasia
(benign vs malignant), they also assess the level of anaplasia (weight or mild).
Thus they help develop prognosis (how bad the disease caused by neoplasia).
Anaplasia is severe worsening the prognosis while Anaplasia lightly fixes it. The
more anaplasia observed, the more malignant neoplasia; The less anaplasia
observed, the more malignant neoplasia.
When cells become more specialized during normal development, they form
very organized relationships with similar cells. The simple membrane epithelial
columnar is one example of a very organized network. This membrane is always
as thick as one cell, the nucleus is always located at the end of the cell that
leaning on the tissue of the tie below it, and its intracellular organellers are
always located in certain locations in cells - they are polarized cells. In the
stomach, simple columnar cells form the complex gland, issue important
digestive enzymes, and form thick slimy (mucus) to protect the cytoplasm and
distorted glands (polarity loss) and the absence of mucous enzymes and
secretion (loss of special functions).
Non-differentiated networks do not show high levels of organization; No special
polarization and function. Because the anaplastic cells are not differentiated
such as normal cells, less polarized antaplastic cells and have fewer special
functions. The worse Anaplasia, the more pollarity and disturbed functions. The
more light anaplasia, the higher the polarity and function. The malignancy of
gastric neoplasia may indicate mixed and distorted glands (polarity loss) and the
absence of enzymes and mucus secretions (loss of special functions).
There are at least six Anaplasia features that can be identified by studying
individual cells both taken from the surface or seen in biopsy specimens.
Multiple criteria of malignancy:
1. Anisocytosis and anisocaryosis (variable shape and size of cytoplasm and
nucleus
2. Abnormal mitosis (high mitosis) in the form of an increase in nuclear
basophyll and cytoplasm (core and cytoplasm looks more blue), an
increase in nucleoli ratio to cytoplasm (very large core and a small
amount.
3. Many nucleolus (not one or two nucleolus there are many),
multinucleation (not one or two core, there are many)
Neoplasia structure
All neoplasia consist of two basic components: (a) Neoplastic cell population, or
parenchym (b) tissue and blood vessels, or stromas.
Microscopically, this double composition is best visualized in epithelial tumors
(such as adenoma and carcinoma) where the epithelium stands out clearly to
the stroma. A malignant epithelial tumor with an abscessful number of
connective tissue is referred to as skirrous carcinoma (hard, hard).
Overweight collagen by fibroblasts of skirrous carcinoma may be a response to
tumor cell products such as epidermal growth factor (EGF). This image shows
squamous cell carcinoma (big arrow) and skirrhous reaction. Instead carcinoma
with a slight tissue tissue is soft or medullary (which means like the marrow)
and thus is referred to as a meduler carcinoma
Cancer that grows rapidly, especially carcinoma tends to experience ulceration
and the surface of tumor nodules can be umbilicated (concave such as navel)
due to ischemic necrosis.
Functionally, the tumor blood vessels are abnormal and many leak so bleeding
and edema occur. After neoplastic cells are identified, it is important to
determine where the cell comes from (from organs or what network) and how
aggressive the cell is.
In many cases, neoplastic cell lineages are often quite clear because neoplasia
tend to reproduce cells and original networks (this applies to neoplasia that are
differentiated well). However, this process can be very challenging when a
tumor differs faster. Neoplasia consisting of non-differentiated cells are often
referred to as carcinoma or sarcoma that do not differentiate, poorly
differentiated, or anaplastic. Anaplasia implies the loss of structural features
and normal cytology, higher levels of malignancy, and often worse prognosis.
Even if neoplasia is anaplastic, it often maintains some special internal cells that
can be used to reveal their identity.
Neoplasia cannot grow more than the size of the pins (1-2mm) except to become
vascularization, vascular endothelial growth factor (VEGF) is secreted by many
types of cells and works on endothelial cells to induce growth, migration, and
formation The endothelial vessels and basic fibroblast growth factors (BFGF)
also induce endothelial growth and migration.
The growth of new blood vessels depends on the balance between stimulants
and inhibitors. Cartilage, for example, produces angiogenesis inhibiting factors
and thus is usually not converted by a growing tumor. For this reason,
OsteosarcaMoma tends not to go through the joints.
Nature of non-stop neoplastic growth. Once a cell is converted into neoplastic
cells, the cell will never be normal again. The growth mechanism of growth in
normal cells is permanently disturbed in neoplastic cells.
The term "active and progressive growth" applies to benign and malignant
neoplasia. It does not apply to hyperplasia or metaplasia because while both of
them show abnormal cell proliferation, the growth is not progressive and stops
when the stimulus triggers removed. Instead, neoplastic cells continue to divide
even when the cause is removed. Neoplasia emerges from changing cells. These
are cells that have undergone changes in their genetic structure which results in
defects in the settings paths that control cell proliferation, homeostasis and
normal cell differentiation. As a result, the morphology of normal networks is
lost and a small number of cells that turn into tumor cells that multiply rapidly.
After the cells that change divide, they continue their inheritance to the
offspring. One cell becomes two, two cells to four, four to eight, and so on,
forming identical mass identical cells - clones.
Some of these cells die because apoptosis and some may be one to differentiate
and breed slowly, while others multiply rapidly. The ruling level of benign cells
is relatively slow. However, if not lifted, neoplasia, even those who are benign,
potentially becoming very large. The growth rate is much faster in malignant
neoplasia. The malignancy becomes great faster than benign neoplasia. The
pathologist looks for cells that divide to assess growth speed. They call these
divider cells "mitotic figure". Many mitotic numbers can be counted in
malignant neoplasia; In most of their benign neoplasia is much less frequent.
When benign benign neoplasia develops, they pressed the network around it.
Tame neoplasia does not penetrate (attack) adjacent networks when growing;
They press into the surrounding network. This growth pattern is known as
expansil growth, such as balloon expansion. When compression occurs,
demarcation is formed between the surrounding tissue and neoplasia.
Sometimes the fibrous tissue bands that surround neoplasia - a capsule -
increase demarcation. The demarcation operation allows appointment of
lesions without much damage surrounding. When they appear from several
surfaces (such as a layer of mouth), benign neoplasia often grow out of the
surface, a pattern known as exophytic growth.
Benign neoplasia almost never attacked the surrounding network; They never
metastasized. When examined under a microscope, benign neoplasia consists of
neoplastic cells that have good differentiated neoplastic ones that resemble
their original tissue; No Anaplasia. Benign neoplasia cells still stick to each
other, they don't roam. Because of its compactness, they do not enter blood
vessels or lymphatics to spread elsewhere. Because their cells don't move,
benign neoplasia is not a hospes killer, instead malignant neoplasia grow
rapidly and has the capacity to attack the surrounding tissue. Because of this
invasive growth pattern, they are not well limited from the surrounding tissue -
there is no division and no capsules. If they appear from a surface.
Malignant neoplasia grows into attacking the tissue below, a pattern called
endophyte growth. Almost all neoplasia have the capacity for metastasis. On
microscopic examination, malignant neoplasia consists of non-differentiated
cells with good anaplasia always exist. Benign neoplasia almost never attacked
the surrounding network; They never metastasized. When examined under a
microscope, benign neoplasia consists of neoplastic cells that have good
differentiated neoplastic ones that resemble their original tissue; No Anaplasia.
Benign neoplasia cells still stick to each other, they don't roam. Because of its
compactness, they do not enter blood vessels or lymphatics to spread elsewhere.
Because their cells don't move, benign neoplasia is not deadly.
Metastasis
Metastasis is a process where primary neoplasia spreads to form secondary
neoplasia. This secondary neoplasia grows apart from primary neoplasia and
emerges from self-plastic cells that are released and transported. Metastasis
represents the most deadly malignancy expression and the most important
attention.
The tendency of malignant neoplasia to spread far is called metastasis (meta- =
change, -stasis = location). Remember, the term does not only refer to the
process of spreading to a distant place, but also in the secondary neoplasia itself.
Metastasis is not as easy as it seems. The attackers must cross the base
membrane and they must slip between the vessel layer cells. While in a blood
vessel, they must avoid, dodge, or when malignant cells spread through the
lymphatic system, they can be filtered and trapped in the lymph nodes and
metastasis sites can begin in regional lymph nodes. The cells that attack
then have to reverse the process and come out of the blood vessels when they
arrive at other organs.
Malignant cells can spread into and along the lymphatic and veins. Because
lymphatic and thin-walled veins are found almost everywhere, it is not
surprising if the attacking cell faces it relatively early. When malignant cells
spread through the lymphatic system, they can be filtered and caught up in the
lymph nodes and metastasis sites can begin in the regional lymph nodes.
Sometimes malignancy comes from the intestinal epithelium and ovaries can
penetrate the walls and membranes of the outer cover (peritoneum).
In this case malicious cells will be shed into peritoneal space, natural body
cavity. When this happens, neoplastic cells can move from their origin to be
implanted on other surfaces in the abdominal cavity. Rarely, malignant cells
can spread into and throughout the arteries. Arteries have walls that are far
thicker than lymphatic and veins. Because the walls are thick, metastasis does
not occur too often.
So far the most important consideration in determining whether the metastasis
will occur is the size of the primary neoplasia. This cannot be enough to be
emphasized: the greater the primary lesion, the more likely the occurrence of
metastasis. As a rule of thumb, the malignancy of more than one centimeter in
diameter (even about a penny) may have invaded the surrounding tissue and it
may have meticulously through lymphatics to the closest lymph nodes
(regional). If the invasion and metastasis want to be prevented, primary lesions
must be found in the earliest stage, of course before one centimeter diameter.
Some malignancies have extraordinary power for metastasis; others don't.
Osteosarkoma, malignant neoplasia bone, earn early. On the other hand,
squamous cell carcinoma is rarely metastasized. This means that each type of
malignancy has its own capacity for metastasis.
A gene has been found in neoplastic cells that direct protein production that
seems to prevent metastasis. If the gene is lost or damaged and the protein
product is not available or insufficient, the metastasis is more prominent. One
day, maybe, missing proteins or damaged genes can be replaced, prevent
metastasis and death. Some organs are often a common metastasis place; While
other organs are not, called "right organs". Heart, lung, brain, and bone marrow
is a common metastasis place; While the heart, spleen, and kidneys don't.
Malignant cells can be transported in the bloodstream as individual cells or cell
lumps. This blob is a means at which the metastasis that is transmitted through
blood occurs. There is a paradox here: a large clot of malignant cells (neoplastic
embolism) less likely to produce metastatic colonies
rather than small lumps. Large clots of malignant cells are too large to pass the
capillary; Their trip was stopped at a thick walled vessel when they were narrow
enough to trap them. On the other hand, small neoplastic embolism is trapped
in smaller diameter vessels with thinner walls; Small neoplastic embolism has a
better chance to penetrate the thin-walled blood vessels.
Neoplasia most often enter the vascular system through thin-walled capillaries,
venula, and lymphatics. Metastasis in turn can produce more metastases (called
secondary metastases). Metastatic neoplastic cells may not be active for years
and suddenly begin to grow, the metastatic process is very inefficient and only a
few biologically neoplastic cell clones are biologically to invade and metastasize.
The invasion and metastasis process is called metastatic cascade. This involves
an important interaction with the extracellular matrix (basic membrane and
interstitial tissue). The method of metastasis as follows:
1. The extracellular matrix invasion is the active process shown in a few
steps. The release of tumor cells from each other through the regulation
of decreasing adhesion molecules (for example, epithelial cadherin).
Local Infiltration (Direct Invasion / Distribution)
2. Through blood vessels (most veins, rare arteries) through lymphatic
nursery in the body cavity (transcoelomic deployment / implantation,
carcinomatosis is attached to matrix components through specific
receptors to the base membrane laminin and through integrin It
functions as a receptor to many extracellular components including
fibronectin.
3. The extracellular matrix degradation through the secretion of proteolytic
enzymes produced by tumor cells or secreted by host cells under the
influence of tumor cells. Examples include type IV and other
metaloproteinase collagenases.
4. Tumor-migration cell migration promoted by two molecular categories:
a). Cleavage products from the extracellular matrix (for example, collagen,
laminin) b). Molecular adhesion on the surface of epithelial cells. Tumor
cells get access to circulation by penetrating the vascular and c sub
mucosa space). Tumor cells stop in a distant place, penetrate the basic
membranes of blood vessels and interact with the extracellular matrix.
