CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer

Naoki Ikenaga, Kenoki Ohuchida, Kazuhiro Mizumoto, Lin Cui, Tadashi Kayashima, Katsuya Morimatsu, Taiki Moriyama, Kohei Nakata, Hayato Fujita, Masao Tanaka

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Abstract

Background & Aims: Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer by producing extracellular matrix and soluble factors. However, the functional heterogeneity of PSCs has not been identified until now. Detailed characterization of the PSCs in human pancreatic cancer would provide a set of potential targets for stroma-directed therapy. Methods: We isolated PSCs from fresh pancreatic ductal adenocarcinoma tissue and sorted them by flow cytometry according to cell surface expression of CD10, which is a stromal prognostic marker for various tumors. We analyzed the functional differences between CD10+ PSCs and CD10- PSCs. Results: Immunohistochemical analysis showed that the frequency of CD10 expression by PSCs was markedly higher in tumor tissue than in normal tissue (33.7% vs 0%, respectively, P = .028). In pancreatic ductal adenocarcinoma, CD10 expression by PSCs was associated with positive nodal metastases (P = .011) and a shorter survival time (P < .001). In vitro coculture experiments showed that CD10+ PSCs promoted the invasiveness of pancreatic cancer cell lines, SUIT-2 and Panc-1 cells more intensively than CD10- PSCs. CD10 + PSCs significantly increased the tumor growth and invasiveness of SUIT-2 cells in a murine cotransplantation model. CD10+ PSCs secreted higher levels of matrix metalloproteinase 3 than CD10- PSCs, and knockdown of matrix metalloproteinase 3 in cocultured PSCs reduced the invasion of SUIT-2 and Panc-1 cells. Conclusions: CD10+ PSCs enhance the progression of pancreatic cancer cells. CD10+ PSCs may be a candidate for selective therapeutic targeting in the treatment of pancreatic cancer.

Original languageEnglish
Pages (from-to)1041-1051.e8
JournalGastroenterology
Volume139
Issue number3
DOIs
Publication statusPublished - Sep 2010

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Pancreatic Stellate Cells
Pancreatic Neoplasms
Matrix Metalloproteinase 3
Adenocarcinoma

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

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CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer. / Ikenaga, Naoki; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Cui, Lin; Kayashima, Tadashi; Morimatsu, Katsuya; Moriyama, Taiki; Nakata, Kohei; Fujita, Hayato; Tanaka, Masao.

In: Gastroenterology, Vol. 139, No. 3, 09.2010, p. 1041-1051.e8.

Research output: Contribution to journalArticle

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T1 - CD10+ pancreatic stellate cells enhance the progression of pancreatic cancer

AU - Ikenaga, Naoki

AU - Ohuchida, Kenoki

AU - Mizumoto, Kazuhiro

AU - Cui, Lin

AU - Kayashima, Tadashi

AU - Morimatsu, Katsuya

AU - Moriyama, Taiki

AU - Nakata, Kohei

AU - Fujita, Hayato

AU - Tanaka, Masao

PY - 2010/9

Y1 - 2010/9

N2 - Background & Aims: Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer by producing extracellular matrix and soluble factors. However, the functional heterogeneity of PSCs has not been identified until now. Detailed characterization of the PSCs in human pancreatic cancer would provide a set of potential targets for stroma-directed therapy. Methods: We isolated PSCs from fresh pancreatic ductal adenocarcinoma tissue and sorted them by flow cytometry according to cell surface expression of CD10, which is a stromal prognostic marker for various tumors. We analyzed the functional differences between CD10+ PSCs and CD10- PSCs. Results: Immunohistochemical analysis showed that the frequency of CD10 expression by PSCs was markedly higher in tumor tissue than in normal tissue (33.7% vs 0%, respectively, P = .028). In pancreatic ductal adenocarcinoma, CD10 expression by PSCs was associated with positive nodal metastases (P = .011) and a shorter survival time (P < .001). In vitro coculture experiments showed that CD10+ PSCs promoted the invasiveness of pancreatic cancer cell lines, SUIT-2 and Panc-1 cells more intensively than CD10- PSCs. CD10 + PSCs significantly increased the tumor growth and invasiveness of SUIT-2 cells in a murine cotransplantation model. CD10+ PSCs secreted higher levels of matrix metalloproteinase 3 than CD10- PSCs, and knockdown of matrix metalloproteinase 3 in cocultured PSCs reduced the invasion of SUIT-2 and Panc-1 cells. Conclusions: CD10+ PSCs enhance the progression of pancreatic cancer cells. CD10+ PSCs may be a candidate for selective therapeutic targeting in the treatment of pancreatic cancer.

AB - Background & Aims: Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer by producing extracellular matrix and soluble factors. However, the functional heterogeneity of PSCs has not been identified until now. Detailed characterization of the PSCs in human pancreatic cancer would provide a set of potential targets for stroma-directed therapy. Methods: We isolated PSCs from fresh pancreatic ductal adenocarcinoma tissue and sorted them by flow cytometry according to cell surface expression of CD10, which is a stromal prognostic marker for various tumors. We analyzed the functional differences between CD10+ PSCs and CD10- PSCs. Results: Immunohistochemical analysis showed that the frequency of CD10 expression by PSCs was markedly higher in tumor tissue than in normal tissue (33.7% vs 0%, respectively, P = .028). In pancreatic ductal adenocarcinoma, CD10 expression by PSCs was associated with positive nodal metastases (P = .011) and a shorter survival time (P < .001). In vitro coculture experiments showed that CD10+ PSCs promoted the invasiveness of pancreatic cancer cell lines, SUIT-2 and Panc-1 cells more intensively than CD10- PSCs. CD10 + PSCs significantly increased the tumor growth and invasiveness of SUIT-2 cells in a murine cotransplantation model. CD10+ PSCs secreted higher levels of matrix metalloproteinase 3 than CD10- PSCs, and knockdown of matrix metalloproteinase 3 in cocultured PSCs reduced the invasion of SUIT-2 and Panc-1 cells. Conclusions: CD10+ PSCs enhance the progression of pancreatic cancer cells. CD10+ PSCs may be a candidate for selective therapeutic targeting in the treatment of pancreatic cancer.

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