Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism

Kathryn M. Ziegler, Robert Considine, Eben True, Deborah A. Swartz-Basile, Henry A. Pitt, Nicholas Zyromski

Research output: Contribution to journalArticle

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Abstract

Introduction: Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Material and methods: Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p <0.05 considered significant. Results: Wild-type preadipocyte CM accelerated Pan02 and TGP-47 cell proliferation relative to control (59 ± 12% and 34 ± 12%, p <0.01, respectively). Knockdown of preadipocyte HGF resulted in attenuated proliferation vs. wild type CM in Pan02 cells (35 ± 5% vs. 68 ± 14% greater than control; p <0.05), but proliferation in TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p <0.05). Inhibition of HGF receptor, c-met, resulted in attenuated proliferation versus control in Pan02 cells, but not TGP-47 cells. Conclusions: These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation.

Original languageEnglish (US)
Pages (from-to)179-184
Number of pages6
JournalInternational Journal of Surgery
Volume28
DOIs
StatePublished - Apr 1 2016

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Hepatocyte Growth Factor
Pancreatic Neoplasms
Adipocytes
Conditioned Culture Medium
Growth
Proto-Oncogene Proteins c-met
Cell Proliferation
Analysis of Variance
Obesity
Neoplasms

Keywords

  • Adipocytes
  • Hepatocyte growth factor
  • Obesity
  • Pancreatic cancer

ASJC Scopus subject areas

  • Surgery

Cite this

Adipocytes enhance murine pancreatic cancer growth via a hepatocyte growth factor (HGF)-mediated mechanism. / Ziegler, Kathryn M.; Considine, Robert; True, Eben; Swartz-Basile, Deborah A.; Pitt, Henry A.; Zyromski, Nicholas.

In: International Journal of Surgery, Vol. 28, 01.04.2016, p. 179-184.

Research output: Contribution to journalArticle

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abstract = "Introduction: Obesity accelerates the development and progression of pancreatic cancer, though the mechanisms underlying this association are unclear. Adipocytes are biologically active, producing factors such as hepatocyte growth factor (HGF) that may influence tumor progression. We therefore sought to test the hypothesis that adipocyte-secreted factors including HGF accelerate pancreatic cancer cell proliferation. Material and methods: Murine pancreatic cancer cells (Pan02 and TGP-47) were grown in a) conditioned medium (CM) from murine F442A preadipocytes, b) HGF-knockdown preadipocyte CM, c) recombinant murine HGF at increasing doses, and d) CM plus HGF-receptor (c-met) inhibitor. Cell proliferation was measured using the MTT assay. ANOVA and t-test were applied; p <0.05 considered significant. Results: Wild-type preadipocyte CM accelerated Pan02 and TGP-47 cell proliferation relative to control (59 ± 12{\%} and 34 ± 12{\%}, p <0.01, respectively). Knockdown of preadipocyte HGF resulted in attenuated proliferation vs. wild type CM in Pan02 cells (35 ± 5{\%} vs. 68 ± 14{\%} greater than control; p <0.05), but proliferation in TGP-47 cells remained unchanged. Recombinant HGF dose-dependently increased Pan02, but not TGP-47, proliferation (p <0.05). Inhibition of HGF receptor, c-met, resulted in attenuated proliferation versus control in Pan02 cells, but not TGP-47 cells. Conclusions: These experiments demonstrate that adipocyte-derived factors accelerate murine pancreatic cancer proliferation. In the case of Pan02 cells, HGF is responsible, in part, for this proliferation.",
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AU - Considine, Robert

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