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Onko (Fach) / x10. Eder (Lektion)
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- Define the major characteristics of lymphatic spreading – what is the difference to spreading through the blood circulation? Permeation: lymphatic vessels lack tight inter-endothelial cell tight junctions, pericytes and a basement membrane. Therefore, tumor-associated lymph vessels form an easy passage for tumor cells to lymph nodes and distant organs.Chemotactic diffusion: Tumor cells can be stimulated by cytokines produced by the lymphatic vessels, which promote chemotactic diffusion of tumor cells into the lymphatic system.Lymphangiogenesis: Tumor cells have the ability to secrete growth factors (e.g. VEGF-C) that induce the formation of new lymphatic vessels.
- What are matrix metallo-proteinases? Define structure and function. Structure? A proteolytic enzyme to enter into the blood vessel. For neutral extracellular proteolysis. e.g. collagenases, stromelysins, gelatinases
- Which are the challenges for a tumor cell in the blood circulation and how do the cells manage to survive? Challenges: Mechanical destruction caused by shear forces. Surveillance by immune cells, particularly NK cells.Survival mechanisms of cancer cells: Platelets as shields: Formation of „tumor cell associated microthrombi“ through aggregation of tumor cells with platelets via tissue factor (the receptor for coagulation factors VIIa and X, which serve as the main initiators of coagulation). High platelet count is associated with decreased survival in breast, colorectal, and lung cancer.
- Metastases frequently occur in specific organs – depending on the location of the primary tumor. Explain the “seed and soil” and the “anatomical hypothesis”. „Seed and Soil“ hypothesis: Some types of cancer show an organ-specific pattern of metastasis: − Breast cancer: bone, liver, brain, lungs − Prostate cancer: bone − Colorectal cancer: liver. some tumor cells (the “seed”) grow preferentially in the microenvironment of select organs (the “soil”) and that metastases result only when the appropriate seed was implanted in its suitable soil. anatomical hypothesis: tumor cells follow the circulatory route draining from the primary tumor and arrest in the first organ encountered which lays “on the way” due to blood-flow patterns.The primary factor that determines the patterns of tumor metastasis is the anatomy of vascular and lymphatic drainage from the site of the primary tumor.
- What are circulating tumor cells and how can they be detected in the blood? positive selection with tumor marker or negative selection to find all “nrmal” cells -> rest CTC. Physical methods - filter because of size - electric field - ficoll gradient
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