Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer

Naoki Yoshida; Atsushi Masamune; Shin Hamada; Kazuhiro Kikuta; Tetsuya Takikawa; Fuyuhiko Motoi; Michiaki Unno; Toru Shimosegawa

doi:10.1016/j.canlet.2017.01.008

Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer

Naoki Yoshida, Atsushi Masamune, Shin Hamada, Kazuhiro Kikuta, Tetsuya Takikawa, Fuyuhiko Motoi, Michiaki Unno, Toru Shimosegawa

Research output: Contribution to journal › Article › peer-review

36 Citations (Scopus)

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.

Original language	English
Pages (from-to)	103-114
Number of pages	12
Journal	Cancer Letters
Volume	390
DOIs	https://doi.org/10.1016/j.canlet.2017.01.008
Publication status	Published - 2017 Apr 1

Keywords

Desmoplasia
FERMT2
Integrin
Pancreatic fibrosis
Stroma

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2017.01.008

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@article{572d6f131d2c4cb797ff0ddb59e9da46,

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.",

keywords = "Desmoplasia, FERMT2, Integrin, Pancreatic fibrosis, Stroma",

author = "Naoki Yoshida and Atsushi Masamune and Shin Hamada and Kazuhiro Kikuta and Tetsuya Takikawa and Fuyuhiko Motoi and Michiaki Unno and Toru Shimosegawa",

note = "Funding Information: This study was supported in part by Grant-in-Aid from the Japan Society for the Promotion of Science (26293171, 26461029, 15H04804), the Pancreas Research Foundation of Japan (to T. Takikawa), the Mitsui Life Social Welfare Foundation (to A. Masamune), and the Smoking Research Foundation (to A. Masamune). The funding agencies had no role in the design of the study or preparation of this manuscript, and will have no influence on the data collection, analysis, and interpretation or manuscript publication. Publisher Copyright: {\textcopyright} 2017 Elsevier B.V.",

year = "2017",

month = apr,

day = "1",

doi = "10.1016/j.canlet.2017.01.008",

language = "English",

volume = "390",

pages = "103--114",

journal = "Cancer Letters",

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T1 - Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer

AU - Yoshida, Naoki

AU - Masamune, Atsushi

AU - Hamada, Shin

AU - Kikuta, Kazuhiro

AU - Takikawa, Tetsuya

AU - Motoi, Fuyuhiko

AU - Unno, Michiaki

AU - Shimosegawa, Toru

N1 - Funding Information: This study was supported in part by Grant-in-Aid from the Japan Society for the Promotion of Science (26293171, 26461029, 15H04804), the Pancreas Research Foundation of Japan (to T. Takikawa), the Mitsui Life Social Welfare Foundation (to A. Masamune), and the Smoking Research Foundation (to A. Masamune). The funding agencies had no role in the design of the study or preparation of this manuscript, and will have no influence on the data collection, analysis, and interpretation or manuscript publication. Publisher Copyright: © 2017 Elsevier B.V.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - 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.

AB - 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.

KW - Desmoplasia

KW - FERMT2

KW - Integrin

KW - Pancreatic fibrosis

KW - Stroma

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U2 - 10.1016/j.canlet.2017.01.008

DO - 10.1016/j.canlet.2017.01.008

M3 - Article

C2 - 28093281

AN - SCOPUS:85010433061

SN - 0304-3835

VL - 390

SP - 103

EP - 114

JO - Cancer Letters

JF - Cancer Letters

ER -

Kindlin-2 in pancreatic stellate cells promotes the progression of pancreatic cancer

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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