EXPRESSION OF UPA AND ITS RECEPTOR BY BOTH NEOPLASTIC AND STROMAL CELLS DURING XENOGRAFT INVASION

Recent studies have shown that molecules involved in generation and re gulation of extracellular proteolytic activity are often expressed by non-malignant stromal cells during human cancer invasion. We have stud ied the expression of the urokinase-type plasminogen activator and the urokinase-type plasminogen activator cell-surface receptor in xenogra fts of human MDA-MB-231 mammary carcinoma cells growing invasively in nude mice. Northern analysis showed the presence of both human and mou se urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor mRNA in tumor extracts. By in situ hybridization, mRNA for human urokinase-type plasminogen activator and its receptor w as detected in virtually all the cancer cells, while mouse urokinase-t ype plasminogen activator and urokinase-type plasminogen activator rec eptor mRNA was expressed by tumor-infiltrating fibroblast-like and mac rophagelike cells. In invasive areas the cells expressing the 2 murine mRNAs were either the same or located immediately adjacent to each ot her. This model system has several advantages for studies of the mecha nism by which cancer cells induce or recruit stromal cells to produce molecules involved in proteolysis. (C) 1994 Wiley-Liss, Inc.