AXL RECEPTOR TYROSINE KINASE EXPRESSION IN PANCREATIC CANCER AND PANCREATIC CANCER CELL LINES.

Abstract

Receptor tyrosine kinases and their ligands play key roles in regulation of cell growth. In this context, receptor tyrosine kinases of the Axl/Tyro3 family together with their ligand growth arrest specific gene 6 (gas6) have shown anti-apoptotic effects, including the mediation of an increased resistance to serum deprivation. We investigated the expression of Axl and the corresponding ligand gas6 in pancreatic cancer in vivo and in vitro to evaluate this receptor/ligand system as potential prognostic or therapeutic marker. Five pancreatic adenocarcinoma specimens, together with corresponding histologically normal pancreatic tissues were examined by immunohistochemistry (IHC) and RT-PCR. 8 pancreatic cancer cell lines were examined by RT-PCR, immunofluorescence, western-blot and immunoprecipitation. Axl receptor tyrosine kinase as well as it’s ligand gas6 were detected in all pancreatic cancer specimens as well as in normal pancreatic tissues by RT-PCR and IHC. In normal pancreatic tissue Axl as well as gas6 was expressed in islets. In 60% (3/5) of pancreatic adenocarcinomas Axl and Gas6 was detected in pancreatic cancer cells. Expression of Axl together with it’s ligand gas6 was confirmed in pancreatic cancer cell lines by RT-PCR. Western-blot analysis indicated a high expression of Axl in 38% (3/8), as well as low expression in 25% (2/8) of the cell lines. Gas6 protein was only detected in cell lines co-expressing the Axl receptor tyrosine kinase protein. Immunofluorescence with anti- Axl located the Axl tyrosine kinase receptor to the cell surface. Co-expression of Axl with its ligand gas6 suggests a possible paracrine mechanism enhancing cell survival. The strong expression of Axl and gas6 in islets of Langerhans would not allow feasible prognostic screening. However, expression of Axl as well as gas6 in pancreatic cancer cells in vivo and in vitro indicates a ligand/receptor system with potential for developing a e.g. antibody based therapeutic approach for therapy of pancreatic cancer.