Serial in vivo loss and in vitro gain of Fas expression and function in human cancerous pancreatic duct cells.

Recent studies have shown the involvement of the Fas system (Fas receptor and its ligand FasL) in cancerous processes. The absence or downregulation of Fas, reported in the majority of human tumors, conflicts with its presence in cancerous cells from the same tumors but maintained in vitro. Recently, the eventual role of environmental factors in the loss of Fas expression, or in the in vivo selection of a Fas-negative cell population has been suggested. We determined the Fas expression and function in the Capan-1 human cancerous pancreatic duct cells over 2 successive passages in vivo separated by a period of 10-20 passages in vitro. We showed that Capan-1 cells express Fas and are sensitive to Fas-mediated apoptosis when maintained in vitro. When these cells were xenografted into nude mice the expression of Fas was lost in the majority of the tumors. Culture of tumor-derived cells exhibited that they became Fas-positive and sensitive to Fas-mediated apoptosis after a short period in vitro. The loss/gain of Fas was reproduced after re-explantation and re-culture of these Fas-expressing cells. Furthermore, RT-PCR evidenced a strong inhibition of Fas, FLICE and FADD mRNAs expression in the xenografts. Our observations indicate that the expression of Fas and its function could depend to factors in the tumoral environment. The in vivo loss of Fas may thus play an important role in the tumor formation and in the evasion of tumor cells from immune surveillance.