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Interactions of Normal, Dysplastic, and Malignant Mammary Epithelial Cells with Fibronectin in Vivo and in Vitro¹

Departments of Pathology, Beth Israel Hospital and Harvard Medical School, and the Charles A. Dana Research Institute, Beth Israel Hospital, Boston, Massachusetts 02215

Previous studies have demonstrated that normal and malignant mouse mammary cells are indistinguishable in many surface-related properties that often denote transformation of other cell types such as fibroblasts. In the present investigation, the interactions of normal, dysplastic, and malignant mammary epithelial cells with fibronectin in tissues and cultures were examined by indirect immunofluorescence. Cells lining the lumina of ducts and alveoli in normal and dysplastic mouse and human mammary tissues abutted a layer of fibronectin along their basal surfaces that included the region of the basement membrane and the underlying stroma. Moreover, double staining for keratin and fibronectin revealed that myoepithelial cells were surrounded by the matrix protein. In contrast, tumor cells in adenocarcinomas and ductal carcinomas were not directly associated with fibronectin. The accumulation of fibronectin in primary cultures prepared from mouse mammary tissues paralleled the distribution seen in vivo. A matrix of fibronectin formed beneath normal and preneoplastic mammary cells within 4 to 6 days after plating, whereas tumor cells were negative, regardless of the age or density of the culture. This correlation with in vivo results did not extend to cells of established mammary tumor culture lines which readily accumulated pericellular networks of fibronectin. Addition of exogenous fibronectin to primary cultures enhanced formation of a basal matrix by normal cells but had no effect on the negative status of the tumor cells. The results indicate that mammary tumor cells in tissues and in primary cultures have an altered capacity to interact with fibronectin. However, this alteration is not necessarily expressed by established mammary tumor cell lines.

¹ Supported by NIH Grant CA 26406 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 10/24/80. Accepted 2/13/81.