Loss of basement membrane deposits and development of invasive potential by virally-transformed rat mammary cells are independent of collagenase production.

Abstract

The myoepithelial-type cell line, Rama 712, derived from a normal rat mammary gland, deposits an extracellular matrix containing type-IV collagen and other basement membrane proteins round its cellular periphery. After transformation with a temperature-sensitive mutant of Rous sarcoma virus (tsRSV) the cells fail to deposit an extracellular matrix at the permissive temperature (35 degrees C), but retain the capacity to do so at the non-permissive temperature (41 degrees C). The synthesis of type-IV collagen is not affected by the temperature shift. Rama 712 cells fail to form tumours in syngeneic rats. However, Rama 712-tsRSV cells form tumours that are locally invasive but fail to metastasize. In histological sections, the tumour cells stain with an antibody to type-IV collagen, but do not deposit any extracellular type-IV collagen. Cells isolated from the tumours (Rama 712T) remain temperature-sensitive for the extracellular deposition of type-IV collagen when grown in vitro. Rama 712, Rama 712-tsRSV and Rama 712T fail to produce any detectable type-I or type-IV collagenase at either 35 degrees C or 41 degrees C. These results show that in this system extracellular deposits of basement membrane proteins are lost from invasive tumours produced by myoepithelial-type cells by mechanisms other than those due to the production of collagenolytic enzymes.