Malignant Progression of Harvey RAS Transformed Normal Human Bronchial Epithelial Cells
Metastasis is a complex process involving the physiology of cellular interactions with environmental factors such as growth factors and biological modifiers, membrane structures, local and humoral immunological effectors1–9. These interactions ordinarily shape the regulatory functions that coordinate the individual role of cells in the tissue and organ system. However, when metastasis occurs the following aberrant events must occur to cause this biological transition: 1) a genetic change in a cell within a primary tumor3 results in at least the following subsequent changes before metastasis of primary tumor cells to distal sites: a) the cell must be capable of growth to produce a clone capable of metastatic expression, b) the cells in this clone produce enzymes that hydrolyze surrounding structures constituting the basement membrane7–15, c) motility permits the cell to escape its local position and move through anatomical barriers to other locations in the host via the circulatory or lymphatic systems11,13,16, d) cells with the potential to develop tumors at distant locations must escape immune surveillance17,18 and e) finally cells from these metastatic clones establish themselves at distal locations and initiate development of a metastasized tumor that damages tissues and organs not associated with the primary tumor site19–24. Interestingly, these processes often involve the spread of primary tumors in a given location along fairly restricted guidelines of anatomical location for metastatic tumors1,5,8. This observation indicates a specificity of biological control of this process and suggests that the mechanisms regulating metastasis must result from specific changes at the genetic level to permit the development of defined phenotypic expression in these events. Therefore, the specific and consistent pattern of metastatic tumor spread suggests the existence of consistently altered genetic pathways that result in the aberrant physiology required to explain the observation of particular and specific patterns of tumor growth and spread during the metastatic phase of cancer.
KeywordsNude Mouse Soft Agar Human Bronchial Epithelial Cell Athymic Nude Mouse Albert Einstein College
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