Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers

L. Mishra, Barbara L. Bass, B. S. Ooi, A. Sidawy, L. Korman, H. Monig

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The identification of novel autocrine/paracrine signaling pathways and possible markers represents an important component in the understanding of tumor growth control. In this study, we assessed the potential role of insulin-like growth factor-I (IGF-I), the IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) in human colorectal cancer. Initial studies demonstrating increased IGF-I binding and IGF-IR density in human colon cancer tissue revealed that a component of iodinated (3-[125- I]iodotyrosyl) IGF-I (125I-IGF-I) binding was not attributable to IGF-IR. Binding studies and Western blot analysis suggested that this second component of 125I-IGF-I binding could be due to IGFBP-2. Further analysis by a specific solution hybridization/RNase protection assay for IGF-IR mRNA levels, IGFBP-2 mRNA levels and in situ hybridization for IGFBP-2 localization, was carried out in nine patients with colon cancer. IGF-IR mRNA levels by RNAse protection assays were unchanged, whereas IGFBP-2 mRNA levels were increased 4-8-fold in patients with colon cancer compared to controls. Three patients with Dukes stage C disease had the highest levels of IGFBP-2 mRNA. In situ hybridization studies localized IGFBP-2 mRNA to malignant cells and not to the surrounding stromal cells, suggesting an autocrine role for IGFBP-2. The discrepancy between increased IGF-I binding, IGF-IR density, IGFBP-2 mRNA and the minimal modulation of the IGF-IR mRNA implies post- transcriptional regulation of IGF-IRs. Our results suggest that IGFBP-2 may be implicated in colon cancer metastases and prognosis. Its usefulness as a potential tumor marker should be further investigated.

Original languageEnglish (US)
Pages (from-to)473-479
Number of pages7
JournalGrowth Hormone and IGF Research
Volume8
Issue number6
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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