Ezrin-expressing lung adenocarcinoma cells and podoplanin-positive fibroblasts form a malignant microenvironment

Shigeki Suzuki, Genichiro Ishii, Rie Matsuwaki, Shinya Neri, Hiroko Hashimoto, Chisako Yamauchi, Keiju Aokage, Tomoyuki Hishida, Junji Yoshida, Mitsutomo Kono, Kanji Nagai, Atsushi Ochiai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Results: The PDPN-CAFs (+) cases had significantly higher rates of node metastasis (p < 0.01) and vascular invasion (p < 0.01). The cancer cells from the PDPN-CAFs (+) cases also had a significantly higher staining score for Ezrin (p < 0.01) than those from the PDPN-CAFs (−) cases. The migration and invasion activities of the shEzrin-induced PC-9 cells were significantly lower than those of the control cells.

Conclusions: Our results indicated that within a tumor microenvironment composed of PDPN-CAFs, increased Ezrin expression in cancer cells might play a key role in the invasiveness of lung adenocarcinoma.

Purpose: Cancer cells and cancer-associated fibroblasts (CAFs) together create the tumor microenvironment, which affects malignant behavior. Lung adenocarcinomas with CAFs expressing podoplanin (PDPN) are clinically aggressive, but the molecular mechanism underlying this phenomenon has not been established. So we identified the characteristic immunophenotype of lung adenocarcinoma cells coexisting with PDPN-expressing CAFs (PDPN-CAFs) and examined how it relates to an aggressive clinicopathological outcome.

Methods: We analyzed the clinicopathological characteristics of 119 adenocarcinomas with a uniform size (2–3 cm). The expression levels of ten invasiveness-related proteins which related to cell adhesion and invasiveness, such as Ezrin, were examined in cancer cells from PDPN-CAFs (+) cases and from PDPN-CAFs (−) cases (n = 20 each). To examine the functional importance of the identified protein on the invasion phenotype, we performed wound healing and a Matrigel invasion assay using shRNA-knockdown lung adenocarcinoma cells (PC-9).

Original languageEnglish
Pages (from-to)475-484
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume141
Issue number3
DOIs
Publication statusPublished - 2014 Jan 1
Externally publishedYes

Keywords

  • CAFs
  • Cancer microenvironment
  • Ezrin
  • Lung cancer
  • Podoplanin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Suzuki, S., Ishii, G., Matsuwaki, R., Neri, S., Hashimoto, H., Yamauchi, C., Aokage, K., Hishida, T., Yoshida, J., Kono, M., Nagai, K., & Ochiai, A. (2014). Ezrin-expressing lung adenocarcinoma cells and podoplanin-positive fibroblasts form a malignant microenvironment. Journal of Cancer Research and Clinical Oncology, 141(3), 475-484. https://doi.org/10.1007/s00432-014-1851-8