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

J Biomed Sci. Nov-Dec 2002;9(6 Pt 2):665-74. doi: 10.1159/000067282.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Autocrine Communication / drug effects*
  • Cell Division / drug effects
  • Drug Interactions
  • Drug Resistance, Neoplasm*
  • Esophageal Neoplasms / chemistry*
  • Esophageal Neoplasms / drug therapy
  • Humans
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / pharmacology*
  • Mice
  • Mice, SCID
  • Phosphorylation
  • Receptor, IGF Type 1 / analysis
  • Transplantation, Heterologous
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Insulin-Like Growth Factor I
  • Receptor, IGF Type 1