Predisposition of subclones of pancreatic carcinoma cells, AsPC-1, to changes in functional and histopathological features of xenograft tumors with response to extracellular matrix

Abstract

We cloned two characteristics subclones from a human pancreatic carcinoma cell line, AsPC-1, according to their distinctive cell shapes; one an epithelial morphology and designated as "Beto-1" and the other a fibroblastic morphology and designated as "Fib-1". Fib-1 grew faster than Beto-1, but the growth rate of the cells on plastics was as high as that of the cells on the extracellular matrix extracts, matrigel. The pancreatic tumor-marker proteins, alpha-amylase, insulin, CEA, POA, PP, and AFP, but not CA 19-9, were positive in both subclones. Type IV collagen, fibronectin, and laminin, were all positive in both subclones; furthermore, the integrin adhesion receptor molecules, alpha 2 beta 1-subunit, alpha 5-subunit, and alpha 6-subunit, were also positive. The intercellular adhesion molecules, E-cadherin and ICAM-1, were detected in Beto-1 and Fib-1, respectively. Although both subclonal cells attached to type IV collagen, fibronectin, and laminin in a concentration-dependent manner. Beto-1 adhered most strongly to type IV collagen and Fib-1 attached most strongly to fibronectin. Beto-1 showed morphological differentiation on matrigel and in the tumor xenografts. Further, there was more fibroblast infiltration and type IV collagen production in Beto-1 tumor tissues, and more lymphocyte and neutrophil infiltration in tumors of Fib-1 which expressed ICAM-1 proteins. This study indicated that the histological diversity observed in the pancreatic carcinoma was evolved from the composition of the tumor cells which express the specific adhesion receptors.