Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer

Jian An, Atsushi Enomoto, Liang Weng, Takuya Kato, Akari Iwakoshi, Kaori Ushida, Keiko Maeda, Maki Ishida-Takagishi, Genichiro Ishii, Shuhong Ming, Tieying Sun, Masahide Takahashi

研究成果: Article査読

20 被引用数 (Scopus)

抄録

Purpose: Cancer-associated fibroblasts (CAFs) contribute to tumor progression through multiple pathways. However, the effect of CAFs on gene expression in lung cancer has been largely unknown. Here we systematically compared the gene expression changes in lung cancer cells induced by normal fibroblasts and CAFs. Methods: Wound healing and cell proliferation assays were used to identify the property of CAFs used in this study. We used cDNA microarray analysis to compare gene expression in lung cancer cells cultured with either conditioned medium (CM) from lung CAFs or normal lung fibroblasts, the result of which was confirmed by RT-PCR and Western blot analysis. Immunohistochemistry on tissue sections from lung cancers was conducted to further confirm the results of cDNA microarray analysis. Results: The expression of many genes was upregulated in cancer cells by CAF CM, particularly cell adhesion molecules, integrins, and anti-apoptotic protein Bcl-2. Expression of integrins appeared to be upstream from Bcl-2. We identified transforming growth factor-β as a candidate factor that induced the expression of those genes in cancer cells. Immunohistochemical studies of clinical lung cancer tissues revealed that integrins and Bcl-2 were more highly expressed in the leading cells (LCs) than in the following cells, at the invasive front of cancer nests, which are adjacent to or in proximity to the stroma. Furthermore, the expression of integrins and Bcl-2 in LCs had a tendency to correlate with the clinical stage of cancer progression, including lymph node metastasis. Conclusions: Our results suggest that CAFs promote lung cancer progression partly through the direct regulation of gene expression in the LCs of invasive cancer nests.

本文言語English
ページ(範囲)379-388
ページ数10
ジャーナルJournal of Cancer Research and Clinical Oncology
139
3
DOI
出版ステータスPublished - 03-2013
外部発表はい

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

フィンガープリント 「Significance of cancer-associated fibroblasts in the regulation of gene expression in the leading cells of invasive lung cancer」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル