RRC ID 67656
Author Suzuki S, Ishii G, Matsuwaki R, Neri S, Hashimoto H, Yamauchi C, Aokage K, Hishida T, Yoshida J, Kohno M, Nagai K, Ochiai A.
Title Ezrin-expressing lung adenocarcinoma cells and podoplanin-positive fibroblasts form a malignant microenvironment.
Journal J Cancer Res Clin Oncol
Abstract 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).
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.
Volume 141(3)
Pages 475-84
Published 2015-3-1
DOI 10.1007/s00432-014-1851-8
PMID 25304618
MeSH Adenocarcinoma / metabolism Adenocarcinoma / pathology* Apoptosis Biomarkers, Tumor / metabolism* Cell Movement Cell Proliferation Cytoskeletal Proteins / metabolism* Female Fibroblasts / metabolism Fibroblasts / pathology* Humans Immunoenzyme Techniques Lung Neoplasms / metabolism Lung Neoplasms / pathology* Lymphatic Metastasis Membrane Glycoproteins / metabolism* Neoplasm Invasiveness Prognosis Tumor Cells, Cultured Tumor Microenvironment* Wound Healing
IF 3.656
DNA material pENTR4-H1 (RDB04395)