Cancer Biology. Metastasis

Cancer Biology. Metastasis - METASTASIS RANDOM DISTRIBUTION...

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METASTASIS RANDOM DISTRIBUTION OF CANCER CELLS THROUGH THE VASCULAR SYSTEM OR GENETICALLY DETERMINED PROCESS OF ACTIVE HOMING?
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PHENOTYPIC CHARACTERISTICS OF CANCER 1. EXCESSIVE GROWTH 2. EXTENSION OF LIFE SPAN 3. METASTASIS FORMATION GENETIC BASIS OF CANCER ONCOGENES (growth factors and receptors, signaling molecules, apoptosis inhibitors) TUMOR SUPPRESSOR GENES (mediators of cell cycle arrest, mediators of apoptosis) DNA REPAIR GENES (sequence fidelity, chromosome stability) controversial SENESCENCE GENES (cell cycle regulators) SENESCENCE SUPPRESSOR GENES (regulators of telomere length)
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Observations that favor passive dyslocation: - according to video microscopy, tumor cells are effectively retained in proximal capillary beds (limited to relatively short time frames of analysis, dependent on the injection of tumor cells) - large size and low deformability of most cancer cells makes passage through small diameter capillaries difficult - tumor cells that disseminate to the lungs stay inside the capillaries for extended periods of time before extravasating (passage to the lungs passive, extravasation rate limiting) - metastatic dissemination is very inefficient and largely limited by apoptosis - individual tumor cells can be found disseminated, and frequently dormant, in peripheral tissues. However, normal cells also can survive in a dormant state for extended periods of time in peripheral tissues (e.g. micro-chimerism of fetal cells in mothers).
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Active locomotion underlying metastasis is supported by: - the number of metastases in specific target organs cannot be accounted for solely by blood or lymph flow patterns - murine experimental melanoma metastasis targets preferentially the lungs, including ectopic lung tissue implanted into the thigh - tumor cells with increased metastatic potential can be selected by repeated passage of cells from the metastatic lesions (metastatic potential is determined by properties of the tumor cells) -specific genes are necessary and sufficient to mediate malignancy (transfection confers invasiveness, gene targeting reduces malignant potential) - homing receptors and their ligands are functionally important in metastasis (cell surface molecules that mediate motility) - the invasive properties by cancer cells are directed by the secretion of extracellular matrix-degrading enzymes (therefore metastasis is an active process) - metastasis suppressor genes negatively regulate invasiveness by genetic programs that are intrinsic to the tumor cells.
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Cancer Biology. Metastasis - METASTASIS RANDOM DISTRIBUTION...

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