Advancing integrated care for older people through EU policy & a European research agenda on integrated care for older people

Pancreatic ductal adenocarcinomas are characterised by a dense connective tissue reaction. To test the hypothesis that stroma components are synthesised and produced by the tumour cells themselves, eight cell lines as well as six xenografted tumours from human ductal adenocarcinomas of the pancreas were examined for the expression of extracellular matrix proteins (ECM), using cDNA probes and antibodies to collagen and xenografted human pancreatic tumours expressed at least one of the examined ECM at the RNA (collagen type IV> laminin = fibronectin = vitronectin> col-lagen type III> undulin> collagen type I) or protein level (collagen type IV = collagen type III> vitronec-tin> laminin> collagen type I = fibronectin> undulin). In nude mouse tumours expression of laminin and collagen I was most pronounced in well-differentiated carcinomas. In a few tumours, collagen type III, vitronectin and undulin were expressed on the luminal side of the neoplastic glands, suggesting loss of normal polar differentiation. Incubation with fetal calf serum modulated ECM RNA levels to a varying extent in all but one cell line (AsPC-1). The results suggest that human pancreatic ductal adenocarcinomas cells are capable of synthesising and producing extracellular matrix proteins in vitro and in vivo, but that the extent and pattern of ECM expression differs between the various tumours and conditions tested. Well-differentiated ductal adenocarcinomas of the pancreas show abundant dense stroma, usually intact basal membranes and regular laminin deposits, while these features are either inconspicuous or even absent in poorly differentiated ductal carcinomas of the pancreas (Kloppel & Fitzgerald, 1986; Kloppel et al., 1985). The factors which determine the stromal development in these pancreatic carcinomas are not known. Immunocytochemical, radioimmunological and biochemical in vivo and in vitro studies have indicated that tumours of epithelial origin, including pancreatic carcinoma, have the potential to produce extracellular matrix proteins and that in cell cultures laminin appears to increase tumour cell polarity and exocytosis (Mollenhauer et al., 1987). As these findings suggest a role for laminin and possibly also other ECM in pancreatic carcinoma differentiation, it is important to know whether the expression of ECM can be indeed traced back to the RNA level of the tumours and correlated to their morphology. Our study therefore addressed the following questions: are ductal pancreatic adenocarcinoma cells capable of producing different components of the extracellular matrix in vitro and in vivo?; is the expression influenced by the degree of tumour differentiation?; and can the expression of ECM …