Podoplanin-expressing cancer-associated fibroblasts inhibit small cell lung cancer growth

Oncotarget. 2015 Apr 20;6(11):9531-41. doi: 10.18632/oncotarget.3371.

Abstract

Cancer-associated fibroblasts (CAFs) expressing podoplanin (PDPN) are a favorable prognosticator in surgically resected small cell lung cancer (SCLC). Here we explore whether CAFs expressing PDPN influence proliferation of SCLC cells. Compared with control group (SCLC cells co-cultured with CAFs-Ctrl), numbers of SCLC cells co-cultured with CAFs overexpressing PDPN were decreased. Suppression of PDPN expression by shRNA in CAFs resulted in increased numbers of SCLC cells. In surgically resected human SCLC specimens, the frequency of Geminin-positive cancer cells was significantly higher in the cases with PDPN-positive CAFs than in the cases with PDPN-negative CAFs. Thus CAFs expressing PDPN inhibit growth of SCLC cells, suggesting that CAFs expressing PDPN represent a tumor inhibitory stromal cell component in SCLC.

Keywords: cancer-associated fibroblasts; podoplanin; small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology
  • Aged
  • Animals
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Small Cell / pathology*
  • Cell Line, Tumor
  • Coculture Techniques
  • Female
  • Fibroblasts / physiology*
  • Geminin / biosynthesis
  • Geminin / genetics
  • Gene Expression Regulation, Neoplastic
  • Graft Survival
  • Heterografts
  • Humans
  • Lung Neoplasms / pathology*
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, SCID
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Stromal Cells / physiology*
  • Transfection
  • Tumor Burden
  • Tumor Microenvironment / physiology*

Substances

  • GMNN protein, human
  • Geminin
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PDPN protein, human
  • RNA, Small Interfering