Coexpression of MUC16 and mesothelin is related to the invasion process in pancreatic ductal adenocarcinoma.
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.
Second Department of Surgery, Wakayama Medical University, Wakayama, Japan.
Atsushi
A
Shimizu
Seiko
S
Hirono
Masaji
M
Tani
Manabu
M
Kawai
Ken-Ichi
K
Okada
Motoki
M
Miyazawa
Yuji
Y
Kitahata
Yasushi
Y
Nakamura
Tetsuo
T
Noda
Shozo
S
Yokoyama
Hiroki
H
Yamaue
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018394:CA-125 Antigen / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D000090204:Mesothelin; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015854:Up-Regulation
D018394:CA-125 Antigen; D058851:GPI-Linked Proteins; C451759:MUC16 protein, human; D008565:Membrane Proteins; D000090204:Mesothelin