Role of epidermal growth factor and its receptor in regulating proliferation of colon cancer stem cells

Yanjun Feng, Qian Liu, Yi Fang, Rongfeng Song, Yiye Wan, Jiansheng Liu, Haiwei Wang, Yanzhi Du, Ji Zhang, Lu Xia

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Cancer stem cells (CSCs) are a subpopulation of cancer cells that can self-renew, multilineage-differentiate and proliferate. Studies have shown that epidermal growth factor (EGF) can promote proliferation of CSCs in many tumors. Aims: To investigate the role of EGF and its receptor (EGFR) in regulating proliferation of colon CSCs. Methods: Colon cancer cell lines HT29 and HCT116 were cultured in serum-free medium and treated with EGF, basic fibroblast growth factor (bFGF) and insulin-like growth factor (IGF). Inhibition of proliferation of tumor cells from colon tumorspheres by EGFR inhibitor gefitinib was measured by MTT assay. Inhibition of formation of tumorspheres by EGFR inhibitor gefitinib and PD153035 was assessed in vitro. Cell apoptosis was detected by flow cytometry. Tumorigenic capacity of colon tumorspheres and cell line was determined in vivo. Expressions of stem cell markers LGR5, Musashi-1 and differentiation marker CK20 in tumorspheres and cell line were detected by real-time PCR. Results: Number of HCT116 tumorspheres in EGF group was significantly higher than those in blank control, bFGF and IGF groups (P<0.05). Gefitinib suppressed proliferation of tumor cells from HCT116 tumorspheres, inhibited tumorsphere formation and induced apoptosis in a concentration-dependent manner. Tumorigenic time of HCT116 tumorspheres was significantly faster and tumor volume was significantly larger than HCT116 cell line (P<0.05). Expressions of LGR5 and Musashi-1 were significantly higher and that of CK20 was significantly lower in tumorspheres than in cell line (P<0.05). Conclusions: EGF can promote formation of tumorspheres of colon cancer cell lines HCT116 and HT29. EGFR inhibitor can inhibit proliferation of colon tumorspheres and induce apoptosis, and the mechanism may be related to the regulation of LGR5, Musashi-1 and CK20.

Original languageEnglish (US)
Pages (from-to)714-719
Number of pages6
JournalChinese Journal of Gastroenterology
Volume18
Issue number12
DOIs
StatePublished - 2013

Keywords

  • Apoptosis
  • Cell proliferation
  • Colon cancer stem cells
  • Colonic neoplasms
  • Epidermal growth factor
  • Tumorspheres

ASJC Scopus subject areas

  • Gastroenterology

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