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33 Cards in this Set
- Front
- Back
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Tumor invasion (Definition) |
Local spread of cancer cells; when malignant tumor cells permeate and dissect through the organ or tissue in which the primary tumor is located; in extreme cases, cancer cells can replace most of the normal tissue of the organ |
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Metastasis (Definition) |
Ability of cancer cells to separate from the primary tumor mass and implant themselves at a discontinuous tissue site |
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Which cancers very rarely metastasize? |
Malignant gliomas of the CNS
Basal carcinomas of the skin |
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Relationship between tumor size/rate of growth and metastasis (and one exception to this rule) |
The larger and more rapidly growing the primary tumor, the more likely it is to metastasize
Exception: malignant melanoma |
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What percentage of newly diagnosed solid cancer patients (excluding basal cell carcinoma of the skin) will present with metastases? |
30% |
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Metastasis reduces possibility of ____ |
Cure |
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What are the 3 pathways of tumor metastasis? |
1) Seeding of body cavities and surfaces
2) Lymphatic spread
3) Hematogenous spread |
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What are the steps involved in tumor metastasis by seeding of body cavities and surfaces? |
1) Malignant neoplasm invades through organ
2) Cancer cells enter open spaces (e.g. abdominal cavity, pelvic cavity, pericardial cavity, joint spaces, etc.)
3) Cancer cells implant ("seed") themselves on surfaces of membranes, organs, and tissues within the space |
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What is the most common route of carcinoma metastasis? |
Lymphatic spread |
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What are the steps involved in tumor metastasis by lymphatic spread? |
1) Cancer cells invade lymphatic vessel
2) Cancer cells travel within lymphatic vessel to the nearest lymph node
3) Cancer cells divide within the lymph node
4) Cancer cells exit the node via the efferent lymphatic
5) Cancer cells spread to more distant nodes within various areas of the body |
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Is the pattern of lymph node spread usually predictable or unpredictable? |
Predictable |
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Why is the pattern of lymph node spread usually predictable? |
It follows the natural route of lymphatic drainage |
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Which lymph nodes do cancers of the upper-outer quadrant of the breast metastasize to first? |
Axillary nodes |
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What is the most common route of sarcoma metastasis? |
Hematogenous spread |
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What type of blood vessel is usually implicated in hematogenous spread of tumor metastases? |
Veins |
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What are the steps involved in tumor metastasis by hematogenous spread? |
1) Cancer cells invade into a vein
2) Cancer cells follow venous blood flow to a discontinuous tissue site |
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What are the two most commonly involved sites for hematogenous spread? |
Lungs (SVC and IVC) and liver (portal vein) |
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What are the two phases of tumor metastasis? |
1) Invasion of ECM
2) Vascular dissemination and homing |
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What are the four steps in tumor invasion of the ECM? |
1) Dissociation of tumor cells from one another
2) Attachment of tumor cells to ECM proteins
3) Degradation of ECM by proteolytic enzymes secreted by tumor cells and cells intrinsic to the ECM (macrophages and fibroblasts)
4) Migration of tumor cells through digested ECM channels to blood or lymphatic vessels |
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What causes tumor cells to dissociate from one another? |
1) Down-regulation of E-cadherin on tumor cell membranes
2) Mutations within the cancer cells' genomes involving the genes for catenins |
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What are "catenins"? |
Proteins that link E-cadherin to a cell's cytoskeleton |
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How do tumor cells attach to the ECM? |
Integrins on the tumor cells bind to basement membrane proteins (laminin, fibronectin, collagen) |
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How do tumor cells differ from normal cells in respect to the number and types of integrins on their membranes? |
Tumor cells have many more integrin receptors (especially laminin receptors) than normal cells
Tumor cells may contain types of integrins not found on normal cells |
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Examples of proteolytic enzymes secreted by tumor cells and intrinsic cells of the EMC (macrophages, fibroblasts) |
Cathespin D
Urokinase plasminogen activator
Matrix metalloproteinases (MMPs) |
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What do matrix metalloproteinases (MMPs) do? |
Digest collagen within the ECM |
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What is the role of protein cleavage products generated by enzymatic proteolysis of the ECM? |
They aid in invasion/metastasis by:
1) Functioning as growth factors for tumor cells
2) Promoting angiogenesis, creating a blood supply for tumor cells
3) Functioning as chemoattractants that promote travel of tumor cells through the ECM |
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Is the ECM an innocent bystander in tumor metastasis? |
No |
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What are the steps involved in vascular dissemination of tumor cells? |
1) Tumor cells invade through vessel walls via proteolytic enzymes
2) Once in the bloodstream, tumor cells aggregate with platelets into small clumps (tumor cell embolus)
3) Tumor embolus flows downstream and eventually adheres to endothelial cell membranes at a distant site
4) Tumor cells burrow through the basement membrane of the vessel
5) Tumor cells enter the tissue, proliferate, develop a vascular supply, and evade host defenses |
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Why do tumor cells aggregate with platelets in the bloodstream? |
To enhance tumor cell survival and implantability |
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Homing (Definition) |
Movement of a tumor embolus to its final destination |
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What factors determine which organ/tissue a tumor embolus will locate? |
1) Pathway of drainage
2) Heterogeneity of both tumor cell adhesion molecules and the ligand molecules on endothelial cells
3) Specific chemokine receptors on cancer cell membranes |
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Why are some tissues naturally impervious to metastasis? Example? |
Due to an "unpermissive environment"
E.g. skeletal muscle |
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What are two chemokine receptors expressed by breast cancer cells? |
CXCR4 and CCR7 |
