Tumor Progression and Metastasis Flashcards
Tumor Progression
- Loosening of intercellular junctions; cancer cells losing their ability to maintain normal communication network from cell to cell- cells losing contact inhibition which enables cells to communicate w/ one another and for the cell to remain stable
- Attachment; cancer cells start forming more specific contacts w/ the basement membrane, especially if these cells are laying on that basement membrane- they start expressing receptors for some of these basement membrane proteins (Laminin receptor, Fibronectin receptor)
- Degradation; cells are starting to make enzymes- gene mutations allowing for metastatic capabilities, meaning that the mutations are creating certain proteins that allow for degradation of surrounding environment (Type IV collagenase)
- Migration; cancer cell going through the basement membrane- can have autocrine motility factors that are being made by these metastatic cells- not all are metastatic at first; some are getting the mutation
Tumor angiogenesis
- Tumors cannot enlarge beyond 1-2 mm w/o being vascularized
- FGF
- VEGF
- Angiogenesis aid in tumor metastasis
Flowchart depicting a simplified scheme of the molecular basis of cancer
Mechanisms of metastasis development within a primary tumor
Invasion of ECM
1- Detachment of tumor cells
2- Attachment of tumor cells to matrix
3- Degradation of ECM
4- Migration of tumor cells
Metastasis Meaning
- Denotes the development of secondary implants discontinuous w/ the primary tumor
Modes of Metastasis
- Lymphatic
- Haematogenous
- Retrograde
- Transcoelomic
Lymphatic Spread
- Transport through lymphatics is the most common pathway for the initial dissemination of carcinomas
- Sarcomas may also use this route
Retrograde Metastasis
- Due to obstruction of the lymphatics by the tumor cells the lymph flow is disturbed and tumor cells spread against the flow of lymph causing retrograde metastasis
- Examples: Cancer of the prostate to the supraclavicular lymph nodes and metastatic deposits from bronchogenic cancer to axillary lymph nodes
Virchows lymph nodes
- Nodal metastasis preferentially to the left supraclavicular lymph nodes from cancers of abdominal organs (e.g. cancers of stomach, colon and gallbladder)
Pattern of Lymph Node Involvement During Metastasis
- Follows the natural routes of lymphatic drainage
- Carcinomas in the upper outer breast quadrants disseminate first to the axillary lymph nodes
- Carcinomas of the inner quadrants drain to the nodes along the internal mammary arteries thereafter to the infraclavicular and supraclavicular nodes
- Regional lymph nodes draining the tumor are invariably involved leading to regional nodal metastasis
*carcinoma of the breast to axillary lymph noes
*carcinoma of the thyroid to lateral cervical lymph nodes
*bronchogenic carcinoma to hilar and paratracheal lymph nodes
Skip Metastasis
- When local lymph nodes are bypassed b/c of venous-lymphatic anastomoses or inflammation or radiation has obliterated the lymphatic drainage
Hematogenous spread
- Typical of sarcomas but is also seen w/ carcinomas. Arteries, w/ their thicker walls, are less readily penetrated than are veins
- Arterial spread may occur, however, when tumor cells pass through the pulmonary capillary beds
Metastatic Cascade: Steps Involved in the Hematogenous spread of a tumor
- Liver and lungs are most frequently involved in hematogenous dissemination
*reason: all portal area drainage flows to the liver, all caval blood flows to the lungs
Common and Uncommon Sites of Blood Borne Metastasis
- Liver, lungs, brain, bone, kidney, adrenals
- Spleen, heart, skeletal muscles do not allow tumor metastasis to grow
- Spleen is unfavourable site due to open sinusoidal pattern which does not allow tumor cells to metastasize
- Limbs, head, neck and pelvis drain blood via vena cava so cancers from these sites metastasize to lungs
Certain Cancers with a Propensity for Invasion of Veins
- Renal cell carcinoma- often invades the branches of the renal vein and then the renal vein itself to grow in a snakelike fashion up the inferior vena cava, sometimes reaching the right side of the heart
- Hepatocellular carcinomas- often penetrate portal and hepatic radicles to grow within them into the main venous channels
General Schema of Events in Chemical Carcinogens
