Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers.
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-ICGF-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.
Mishra
L
L
Department of Medicine, Department of Veterans' Affairs Medical Center and Georgetown University Medical Center, Washington DC 20422, USA.
Bass
B
B
Ooi
B S
BS
Sidawy
A
A
Korman
L
L
D001345:Autoradiography; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007457:Iodine Radioisotopes; D012333:RNA, Messenger / Q000235:genetics; D011869:Radioligand Assay; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D018971:Insulin-Like Growth Factor Binding Protein 2; D007457:Iodine Radioisotopes; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1