PURPOSE AND EXPERIMENTAL DESIGN: Insulin-like growth factors (IGFs) I and II and their principle receptor, IGF-I receptor (IGF-IR), are frequently expressed in human colon cancers and play a role in preventing apoptosis, enhancing cell proliferation, and inducing expression of vascular endothelial growth factor (VEGF). To elucidate the in vitro and in vivo effects of IGF-IR in human colon cancer growth and angiogenesis, HT29 cells were transfected with a truncated dominant-negative (DN) form of IGF-IR or vector alone. RESULTS: IGF-I increased VEGF expression in parental and vector-transfected cells, whereas IGF-I induction of VEGF mRNA and protein was abrogated in IGF-IR DN cells. The IGF-IR DN cells demonstrated inhibited growth in both monolayer culture and soft agar (P < 0.05). s.c. injections of IGF-IR DN cells in nude mice led to significantly decreased tumor growth (P < 0.05). Immunohistochemical analyses revealed that IGF-I DN tumors demonstrated decreased tumor cell proliferation, VEGF expression, and vessel count and increased tumor cell apoptosis (P < 0.05 for all parameters compared with controls). Furthermore, IGF-IR DN-transfected cells yielded significantly decreased tumorigenicity and growth in the liver. CONCLUSIONS: These studies demonstrate that the IGF ligand-receptor system plays an important role in multiple mechanisms that mediate human colon cancer growth including regulation of VEGF and angiogenesis.
PURPOSE AND EXPERIMENTAL DESIGN:Insulin-like growth factors (IGFs) I and II and their principle receptor, IGF-I receptor (IGF-IR), are frequently expressed in humancolon cancers and play a role in preventing apoptosis, enhancing cell proliferation, and inducing expression of vascular endothelial growth factor (VEGF). To elucidate the in vitro and in vivo effects of IGF-IR in humancolon cancer growth and angiogenesis, HT29 cells were transfected with a truncated dominant-negative (DN) form of IGF-IR or vector alone. RESULTS:IGF-I increased VEGF expression in parental and vector-transfected cells, whereas IGF-I induction of VEGF mRNA and protein was abrogated in IGF-IR DN cells. The IGF-IR DN cells demonstrated inhibited growth in both monolayer culture and soft agar (P < 0.05). s.c. injections of IGF-IR DN cells in nude mice led to significantly decreased tumor growth (P < 0.05). Immunohistochemical analyses revealed that IGF-I DN tumors demonstrated decreased tumor cell proliferation, VEGF expression, and vessel count and increased tumor cell apoptosis (P < 0.05 for all parameters compared with controls). Furthermore, IGF-IR DN-transfected cells yielded significantly decreased tumorigenicity and growth in the liver. CONCLUSIONS: These studies demonstrate that the IGF ligand-receptor system plays an important role in multiple mechanisms that mediate humancolon cancer growth including regulation of VEGF and angiogenesis.
Authors: Sripriya Raman; Adda Grimberg; Steven G Waguespack; Bradley S Miller; Charles A Sklar; Lillian R Meacham; Briana C Patterson Journal: J Clin Endocrinol Metab Date: 2015-04-03 Impact factor: 5.958
Authors: Yi Peter Hu; Sandip B Patil; Michelle Panasiewicz; Wenhui Li; Jennie Hauser; Lisa E Humphrey; Michael G Brattain Journal: Cancer Res Date: 2008-10-01 Impact factor: 12.701
Authors: Oliver Stoeltzing; Wenbiao Liu; Fan Fan; Christine Wagner; Kathrin Stengel; Ray J Somcio; Niels Reinmuth; Alexander A Parikh; Daniel J Hicklin; Lee M Ellis Journal: Cancer Lett Date: 2007-10-22 Impact factor: 8.679