TY - JOUR
T1 - Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers
AU - Mishra, L.
AU - Bass, B.
AU - Ooi, B. S.
AU - Sidawy, A.
AU - Korman, L.
AU - Monig, H.
N1 - Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032467399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032467399&partnerID=8YFLogxK
U2 - 10.1016/S1096-6374(98)80300-6
DO - 10.1016/S1096-6374(98)80300-6
M3 - Article
C2 - 10985759
AN - SCOPUS:0032467399
VL - 8
SP - 473
EP - 479
JO - Growth Hormone and IGF Research
JF - Growth Hormone and IGF Research
SN - 1096-6374
IS - 6
ER -