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Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Insulin-like growth factor I (IGF-I) receptor (IGF-IR)-mediated signals are known to be involved in cell growth and transformation and prevention of apoptosis. In this study, we demonstrated the coexpression of IGF-I and IGF-IR in human esophageal carcinoma tissues. We also demonstrated the IGF-I autocrine system in esophageal carcinoma cell lines. Both the CE48T/VGH and CE81T/VGH cell lines showed proliferative responses to IGF-I stimulation. Autokinase activity of IGF-IR in these cells can be triggered by the exogenous addition of IGF-I. In addition, an IGF-I peptide antagonist, JB1, specifically inhibited ligand-induced receptor autophosphorylation in a dose-dependent manner. Under serum-free conditions, JB1 also reduced the degree of IGF-IR phosphorylation and cell numbers. Furthermore, the addition of JB1 decreased the number of CE81T/VGH colonies formed in methyl cellulose agar and the size and the incidence of tumors which grew in mice with severe combined immunodeficiency. These results imply that an IGF-I autocrine system in human esophageal carcinoma cells could stimulate tumor growth. Finally, we found that IGF-I prevented the apoptosis of CE81T/VGH cells induced by chemotherapeutic drugs, such as cisplatin, 5-fluorouracil and camptothecin. Thus, interruption of IGF-IR function may provide a way to retard tumor growth and increase the sensitivity of esophageal carcinoma to chemotherapy.

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Authors and Affiliations

  1. Department of Medical Research and Education, Veterans General Hospital-Taipei, 112, Taipei, Taiwan (ROC)

    Wan-Shung Fong, Chungming Chang & Cheng-po Hu PhD

  2. Institute of Microbiology and Immunology, Taiwan, ROC

    Young-Chau Liu, Chuen-Miin Leu, Shan-Chun Chen, Chungming Chang & Cheng-po Hu PhD

  3. Institute of Public Health, National Yang-Ming University, Taipei

    Fen-Hwa Wong

  4. College of Liberal Education, Shu-Te University, Kaohsiung, Taiwan, ROC

    Young-Chau Liu

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Liu, YC., Leu, CM., Wong, FH. et al. Autocrine stimulation by insulin-like growth factor I is involved in the growth, tumorigenicity and chemoresistance of human esophageal carcinoma cells. J Biomed Sci 9, 665–674 (2002). https://doi.org/10.1007/BF02254995

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  • DOI: https://doi.org/10.1007/BF02254995

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