Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma

Cancer Science - Tập 103 Số 4 - Trang 739-746 - 2012
Atsushi Shimizu1, Seiko Hirono2, Masaji Tani2, Manabu Kawai2, Ken‐ichi Okada2, Motoki Miyazawa2, Yuji Kitahata2, Yasushi Nakamura3, Tetsuo Noda4, Shozo Yokoyama2, Hiroki Yamaue2
1Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
2Second Department of Surgery Wakayama Medical University Wakayama
3Department of Clinical Laboratory Medicine, Wakayama Medical University, Wakayama.
4Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan

Tóm tắt

The invasion process is a crucial step for pancreatic ductal adenocarcinoma (PDAC); however, the genes related to invasion remain unclear. To identify specific genes for the invasion process, we compared microarray data for infiltrating cancer and PanIN‐3, which were harvested from an individual PDAC patient by microdissection. Furthermore, immunohistochemical, coimmunoprecipitation and invasion analyses were performed to confirm the biologic significance of molecules identified by expression profile. In the present study, we focused on MUC16 and mesothelin among 87 genes that were significantly upregulated in infiltrating components compared to PanIN‐3 in all PDAC patients, because MUC16 was the most differently expressed between two regions, and mesothelin was reported as the receptor for MUC16. Immunohistochemical analysis revealed that MUC16 and mesothelin were expressed simultaneously only in infiltrating components and increased at the invasion front, and binding of MUC16 and mesothelin was found in PDAC by immunoprecipitation assay. The downregulation of MUC16 by shRNA and the blockage of MUC16 binding to mesothelin by antibody inhibited both invasion and migration of pancreatic cancer cell line. MUC16 high/mesothelin high expression was an independent prognostic factor for poor survival in PDAC patients. In conclusion, we identified two specific genes, MUC16 and mesothelin, associated with the invasion process in patients with PDAC. (Cancer Sci 2012; 103: 739–746)

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Cancer Science

Tập 103 Số 4

739-746

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