KERATINOCYTE GROWTH FACTOR AND ITS RECEPTOR CORRELATE WITH VENOUS INVASION VIA MATRIX METALLOPROTEINASE-9 (MMP-9) IN PANCREATIC CANCER

Abstract

Background: MMP-9 is known to participate in the degradation of type IV collagen, which is one of the major components of vascular basement membranes, and expression of MMP-9 has been associated with venous invasion and hematogenous metastasis in various cancer tissues. We previously reported that co-expression of KGFR and KGF in pancreatic cancer showed a significant association with venous invasion and poor prognosis. In the present study, we investigated the expression of KGFR, KGF and MMP-9 in pancreatic cancer cell lines and their correlations with clinicopathological factors in human pancreatic cancer tissues. Methods: Expression of KGFR, KGF and MMP-9 were examined in eight of human pancreatic cancer cell lines. Immunohistochemical analyses using anti-KGFR, KGF or MMP-9 antibodies were performed on fifty-three cases of pancreatic cancer. Moreover, the correlation with KGFR, KGF or MMP-9, and clinicopathological factors in pancreatic cancer cases was evaluated. Results: KGFR and MMP-9 mRNA were detected in all pancreatic cancer cell lines. In contrast, KGF mRNA was detected in 7 of 8 pancreatic cancer cell lines. KGFR, KGF and MMP-9 were localized in pancreatic cancer cells in 22 of the 53 cases (41.5%), 18 of the 53 cases (34.0%) and 22 of the 53 cases (41.5%), respectively. Clinicopathologically, KGFR, KGF or MMP-9 expression was highly correlated with venous invasion. Moreover, co-expression of KGFR and KGF correlated significantly with venous invasion, MMP-9 expression and poor prognosis. However, survival rates of the MMP-9-positive group and MMP-9-negative group were not significantly different. Conclusion: These findings suggest that co-expression of KGFR and KGF might play an important role in enhancing venous invasion via MMP-9 in pancreatic cancer cases. KGF/KGFR system may lead to the development of new therapeutic strategies for human pancreatic cancer.