title: Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer.
abstract: Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined. SUIT-2 pancreatic cancer cells were subcutaneously injected into nude mice alone or with PSCs and the size of the tumors was monitored. Kindlin-2 expression was observed in PDAC and the peritumoral stroma. Stromal kindlin-2 expression was associated with shorter recurrence-free survival time after R0 resection. Knockdown of kindlin-2 resulted in decreased proliferation, migration, and cytokine expression in PSCs. The PSC-induced proliferation and migration of pancreatic cancer cells were suppressed by kindlin-2 knockdown in PSCs. In vivo, co-injection of PSCs increased the size of the tumors, but this effect was abolished by kindlin-2 knockdown in PSCs. In conclusion, kindlin-2 in PSCs promoted the progression of pancreatic cancer.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshida
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan. Electronic address: amasamune@med.tohoku.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Hamada
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kikuta
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Takikawa
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Fuyuhiko
authors.initials: F
authors.lastname: Motoi
authors.affiliation: Division of Hepato-Biliary-Pancreatic Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Unno
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D058954:Pancreatic Stellate Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: C477322:FERMT3 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins
keywords: Desmoplasia; FERMT2; Integrin; Pancreatic fibrosis; Stroma