Renal cell carcinomas and pancreatic adenocarcinomas produce nidogen in vitro and in vivo

The production of nidogen by four renal cell carcinoma (RCC) and three panc reatic adenocarcinoma (PAc) cell lines has been studied in cell culture and in xenografted tumours in nude mice. In RCC cells, immunoreactivity for ni dogen was seen only after exposure to monensin to induce cytoplasmic accumu lation of secretory proteins. In PAc cells, immunoreaction was also detecta ble in control cells, Immunoblotting of control and monensin-exposed cells and immunoprecipitation of culture media of radioactively labelled cells de monstrated the production of nidogen polypeptide of M-r ca, 150 000 by six of the seven cell lines. Basement membranes (BMs) and stroma of the xenogra fted tumours derived from these six cell lines demonstrated immunoreactivit y for both human and mouse nidogen, as revealed with species-specific antib odies. The ability of the cells to produce nidogen in vitro and deposit in vivo was positively correlated with high histological grade of the xenograf ted tumours, although the small number of cell lines studied calls for furt her studies to confirm this. The distribution of nidogen in human RCC and P Ac specimens was also studied by immunohistochemistry. There was strong imm unoreactivity for nidogen in tumour stroma, BM of carcinoma cell nests, and endothelial basal lamina, but no conclusions could be drawn regarding hist ological grade and immunostaining patterns, because stromal production coul d not be ruled out, The results show that nidogen is produced by human carc inoma cells both in vitro and in vivo. Copyright (C) 1999 John Wiley & Sons , Ltd.