Mechanism of mammary duct stimulation by tumor transplants.

Subcutaneous epithelial Ehrlich ascites tumor (EAT) transplants stimulate adja cent mammary duct epithelium in C57BL mice. Present data describe a similar effect for Sarcoma 180, which is of connective tissue origin. Increased mitotic activity, with peak value on the 2d day of tumor growth, occurred in the epithelial cells of mam mary ducts located in a 1-mm. area around the tumor nodule. Inward proliferation and enlargement of mammary duct cells resulted in increased height of epithelial lining and obliteration of duct lumen. The role of individual tumor components, namely, the ascitic fluid, the tumor cells, the necrotic and connective tissue, was de termined. Ascitic fluid, devoid of tumor cells, had no effect on mammary duct epi thelium. Nor was ascitic fluid required for growth of EAT cells, since saline-washed cells grew as usual and stimulated adjacent mammary duct epithelium. In vitro irradi ation of tumor cells, which inhibited cell multiplication but not cell metabolism, de creased but did not eliminate the capacity of tumor cells to stimulate mammary duct cells. Implants of necrotic tissue did not affect adjacent mammary ducts significantly; nor did the connective tissue capsule, which surrounded transplants of boiled tumor cells, have any significant effect on adjacent mammary duct epithelium. Severe con nective tissue proliferation and damage, as induced by paraffin pellets, did, how ever, produce a high mitotic activity in mammary duct cells, but only in those ducts which were in direct contact with the area of damage. Failure of EAT cells, growing in the vaginal wall of ovariectomized mice, to induce cornification of the overlying vaginal epithelium suggested that mammary duct stimulation by tumor transplants was not due to a local secretion of estrogen by the tumor cells. These results suggested that living, but not necessarily dividing, tumor cells were required for mammary duct stimulation.