ESTABLISHMENT OF A HUMAN HEPATIC ADENOSQUAMOUS CARCINOMA CELL-LINE (KMC-2) AND ITS RESPONSE TO CYTOKINES

A human hepatic adenosquamous carcinoma cell line (KMC-2) was establis hed from a serially transplanted tumor in nude mice (nuKMC-2), which o riginated from human cholangiocellular carcinoma and showed histologic al alteration from adenocarcinoma to squamous cell carcinoma (SCC) alo ng with serial transplantation. KMC-2 cells in monolayer culture proli ferated in a sheet-like arrangement with a population doubling time of 29.5 h, whereas the cells in 0.1% collagen gel embedded culture forme d a compact and tubular structure with the population doubling time of 35.4 h. The cells secreted carbohydrate antigen 19-9 (CA19-9), tissue polypeptide antigen and SCC-related antigen. The back-transplanted nu de mouse turner exhibited morphologic features of adenosquamous carcin oma resembling those in the original nude mouse tumor. IFN-alpha, IFN- gamma and TNF-alpha suppressed cell proliferation significantly. Funct ionally, IFN-gamma significantly suppressed CA19-9 secretion, and conv ersely promoted SCC-related antigen secretion. These findings suggest that KMC-2 is the first human hepatic adenosquamous carcinoma cell lin e primarily originated from adenocarcinoma; the environmental factors, such as the presence of extracellular matrix and the cytokines influe nced the growth, morphology end function of KMC-2.