Cancer metastasis is the process where cancer cells spread from the primary tumor to distant sites in the body. There are 5 major steps in metastasis: 1) invasion of surrounding tissue, 2) release into circulation, 3) survival in circulation, 4) arrest in capillaries of distant organs, 5) penetration of vessel walls and growth. Metastasis can occur through the bloodstream (hematogenous), lymphatic system, or body cavities. Cancer cells degrade the extracellular matrix using enzymes to migrate, and can die from detachment, damage in vessels, or immune system attack. Some cancers have preferential metastatic sites thought to be due to anatomical proximity or a compatible tissue environment.

1. metastasis
ali hatami
ehsan arabi
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2. What is cancer metastasis?
 Cancer defines as a population of cells that
have lost their normal controls of growth and
differentiation and are proliferating without
check
 Metastasis is the process by which a tumor
cell leaves the primary tumor, travels to a
distant site via the circulatory system, and
establishes a secondary tumor
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4. 5 major steps in metastasis
1. Invasion and infiltration of surrounding normal
host tissue
2. Release of neoplastic cells
3. Survival in the circulation
4. Arrest in the capillary beds of distant organs
5. Penetration of the lymphatic or blood vessel
walls followed by growth of the disseminated
tumor cells
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7. Metastatic Growth in the Liver
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8. Routes of Metastasis
 Through the circulatory (blood) system
(hematogenous)
 Through the lymphatic system
 Through the body wall into the
abdominal and chest cavities
(transcoelomic)
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9. Cell movement
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10. a) Matrix degrading enzymes
 Required for a controlled degradation
of components of the extracellular
matrix (ECM)
 The proteases involved in this process
are classified into serine-, cysteine-,
aspartyl-, and metalloproteinase.
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11. Matrix metalloproteinases (MMP)
 16 members, subdivided into 4 groups, based
on their structural characteristics and
substrate specificities
 Soluble and secreted groups; collagenase,
gelatinase and stromelysins
 Membrane type (MT-MMP) group are
anchored in the plasma membrane
 A zinc ion in the active centre of the protease
is required for their catalytic activities.
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12. MMP family
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13. Serine proteases
 Serine protease involved in ECM degradation are
plasmin, plasminogen activators and cathepsin G.
 Plasmin is believed to be the most important serine
protease, firstly because its ability to degrade several
matrix components like gelatin, fibronectin or laminin,
and secondly by the possible activation of numerous
proforms of MMPs by propeptide cleavage.
 Plasmin is synthesized in its inactive proform,
plasminogen, which can be converted to plasmin by
plasminogen activator.
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14. Migrating cancer cells can die from a
variety of causes
 Detachment from the surface of other cells can
lead to cell death (called anoikis 'an-oh-e-kus')
 When Cancer cells travel through the vessels
they can get damaged or stuck, leading to cell
death
 Cancer cells can be recognized and destroyed
by cells of the immune system
 The cells may exist at locations far from the
original tumor without multiplying enough to
cause any problems
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15. Reason for organ selectivity
Anatomic theory: secondary tumors
occur in the organs which they
encounter first during their
dissemination from the primary
tumor
“Seed and soil” theory: the provision of
a fertile environment in which
compatible tumor cells could grow
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16. Preferential metastatic sites
Primary tumour
Common distant site (s)
Breast’ adenocarcinoma
Bone, brain, adrenal
Prostate adenocarcinoma
Bone
Lung small cell carcinoma
Bone, brain, liver
Skin cutaneous melanoma
Brain, liver, Bowel
Thyroid adenocarcinoma
Bone
Kidney clear cell carcinoma
Bone, liver, thyroid
Testis carcinoma
Liver
Bladder carcinoma
Brain
Neuroblastoma
Liver, adrenal
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