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The cytoskeleton in cultured cells: coordinate in vitro regulation of cell growth and shape.

Adenopolyposis of the colon and rectum (ACR) links the well-characterized phenomena of murine oncogenic virus transformation with the progression of a human cancer. The same syndrome links defects in fibroblast growth control and cytoskeletal organization to a tumor of epithelial origin. Since skin fibroblasts are involved in this colonic tumor, the syndrome is very likely to be systemic. That is, one element of normal growth regulation of epithelial cells in situ may be provided by the fibroblasts residing beneath their basement membrane. These observations have led to a novel approach to early detection of persons at risk for a tumor, via the behavior of their skin fibroblasts in culture. At present, it is rarely possible to detect persons at risk for malignancy before the appearance of a frank invasive or metastatic growth. Although many biochemical assays have been proposed as indicators of pre-malignant states or cryptic early tumors, most have eventually been shown to be related to age, sex drug treatment, or other variables linked to but not clearly indicative of, a malignancy. Two serious problems limiting attempts to detect preneoplastic states or a disposition to eventual neoplasia are the inherent low frequency of incidence of any single type of tumor and the difficulty of obtaining identical sample material from prospective or actual patients once they are located. Our approach to these problems significantly departs from the common dependence upon isolation of cells from the site of a tumor. Clearly, it is an easier task to scan skin fibroblasts for disrupted cytoskeletal patterns than it is to obtain epithelia cells from most tissues at high risk for malignancy. This line of work, buttressed by information derived from the model system of SV40 transformation, may provide a novel mode of early detection of other human malignancies, as it has for ACR.