EXPRESSION AND ROLE OF LUMICAN IN PANCREATIC CANCER CELLS AND STROMAL TISSUES

Abstract

Background: Lumican is a member of the small leucine-rich proteoglycan family and is overexpressed during the wound healing process in the cornea and in human breast, colon and pancreatic cancer. In breast cancer tissues, lumican mRNA is overexpressed in stromal fibroblasts but not in cancer cells. The high expression level of lumican in stromal tissues is associated with a high pathological tumor grade, low estrogen receptor levels and young patient age. In the present study, we attempted to clarify whether lumican overexpression affects the clinicopathological features of pancreatic cancer. Methods: Lumican protein expression was examined in MIA-PaCa-2, Panc-1, PK-45H and PK-8 pancreatic cancer cell lines by Western blot analysis. Immunohistochemical analysis with anti-lumican antibody was performed in 54 pancreatic cancer cases. Lumican immunoreactivity in the pancreatic cancer cells and stromal tissues were estimated and the correlation of lumican expression and clinicopathological factors, and prognosis were examined. Results: Lumican protein was detected in pancreatic cancer cell lines. Immunohistochemically, lumican was localized in the alpha cells of islets in control pancreas. In chronic pancreatitis-like lesions adjacent to cancer cells, lumican was localized in acinar and islet cells. In 18 of 56 cases (33%), lumican was strongly expressed in the cytoplasm of cancer cells. In stromal tissue close to cancer cells, lumican was localized in 36 of 56 cases (71%). The overall survival rate was worse in patients showing lumican-negative cytoplasm in cancer cells than for patients with lumican-positive cancer cells. In contrast, lumican in stromal tissues close to cancer cells correlated with retroperitoneal and duodenal invasion and the overall survival rate was worse for patients with lumican-positive stroma than for patients with lumican-negative stroma. Conclusion: Lumican in pancreatic cancer cells and stromal tissues may play different roles in cancer cell growth and invasion.