Proliferation and differentiation of a human colon cancer cell line (CaCo2) is associated with significant changes in the expression and secretion of insulin-like growth factor (IGF) IGF-II and IGF binding protein-4: role of IGF-II.
TLDR
The studies suggest that differential expression of IGF-II and IGFBPs may be playing a critical role in both proliferation and differentiation of colonocytes, and suggested that CaCo2 cell differentiation may require an attenuation ofIGF-II effects.Abstract:
The extent to which the insulin-like growth factor (IGF) system contributes to the initiation and progression of colon cancer remains poorly defined. We recently reported that a majority of human colon cancers express and secrete the potent mitogen IGF-II and at least two inhibitory binding proteins, IGFBP-2 and IGFBP-4. In the present study we measured the expression and secretion of IGF-II, IGFBP-2, and IGFBP-4 in relation to growth and differentiation of CaCo2 human colon cancer cells, which undergo spontaneous enterocytic differentiation in culture. Under the conditions of the present study, CaCo2 cells demonstrated an initial rapid phase of growth between Day 2 through days 7-9 of culture, followed by a significant retardation in the growth between days 9-13. Alkaline phosphatase (ALP) activity, a marker of enterocytic differentiation, progressively increased between Days 7-13 in culture, temporally correlating with post-confluent phase of negligible growth. These changes in growth and differentiation were accompanied by > 80% decline in the relative concentration of IGF-II messenger RNA (mRNA) between Days 2-13. In contrast, the relative mRNA concentrations of inhibitory binding proteins (IGFBP-2 and IGFBP-4) increased rapidly to 200% of Day 2 values by Days 5-7 before returning to baseline levels by Day 13. The relative protein concentrations of the three factors measured in the conditioned media of the cells followed a pattern very similar to that measured for the mRNA levels. While the changes in the relative protein concentrations and mRNA levels of IGF-II and IGFBP-4 were statistically significant, the changes measured in the RNA and protein levels of IGFBP-2 were not, as a result of large inter experimental variations. Thus these results suggested that CaCo2 cell differentiation may require an attenuation of IGF-II effects. To confirm the latter possibility, additional studies were conducted with a specific neutralizing antibody against IGF-II. Incubation of CaCo2 cells with anti-IGF-II antibodies from Day 0 through Day 7 significantly retarded the growth of the cells and was accompanied by a significant increase in the concentration of Alkaline phosphatase activity per 10(6) cells. Recently, we reported a potent inhibitory role of IGFBP-4 in the growth of colon cancer cells. In the present studies, a possible important role of IGF-II is illustrated not only in the growth but also in the differentiation of colonic cells. Our studies thus suggest that differential expression of IGF-II and IGFBPs may be playing a critical role in both proliferation and differentiation of colonocytes.read more
Citations
More filters
Journal ArticleDOI
Role of the insulin-like growth factor family in cancer development and progression
Herbert Yu,Thomas E. Rohan +1 more
TL;DR: Evidence suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth.
Journal ArticleDOI
Prospective Study of Colorectal Cancer Risk in Men and Plasma Levels of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3
Jing Ma,Michael Pollak,Edward Giovannucci,June M. Chan,Yuzhen Tao,Charles H. Hennekens,Meir J. Stampfer +6 more
TL;DR: Ass associations of plasma levels of IGF-I and IGFBP-3 with the risk of colorectal cancer are suggested to be consistent during the first and the second 7-year follow-up intervals and among younger and older men.
Journal ArticleDOI
Calorie Restriction, Aging, and Cancer Prevention: Mechanisms of Action and Applicability to Humans*
TL;DR: This review synthesizes the key biological mechanisms underlying many of the beneficial effects of CR, with a particular focus on the insulin-like growth factor-1 pathway and some of the opportunities now available for investigations.
Journal ArticleDOI
Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro.
TL;DR: The data suggest that IL-8 acts as an autocrine growth factor for colon carcinoma cell lines and would support the concept that a similar autocrine loop operates in vivo.
Journal ArticleDOI
Calories and carcinogenesis: lessons learned from 30 years of calorie restriction research
Stephen D. Hursting,Stephen D. Hursting,Sarah M. Smith,Laura M. Lashinger,Laura M. Lashinger,Alison E. Harvey,Susan N. Perkins +6 more
TL;DR: The evidence on key biological mechanisms underlying many of the beneficial effects of CR are synthesized, with particular emphasis on the impact of CR on growth factor signaling pathways and inflammatory processes and on the emerging development of pharmacological mimetics of CR.
References
More filters
Journal ArticleDOI
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
TL;DR: A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described, providing a pure preparation of undegraded RNA in high yield and can be completed within 4 h.
Journal Article
Enterocyte-like differentiation and polarization of the human colon carcinoma cell line Caco-2 in culture
Journal ArticleDOI
The insulin-like growth factors.
W. S. Cohick,David R. Clemmons +1 more
TL;DR: The ubiquitous distribution of the IGFs, IGFBPs, and IGF receptors indicates that they may play a role in the regulation of coordinate growth among several tissues and cell types and should greatly enhance the understanding of normal growth and development.
Journal ArticleDOI
Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5 and -6).
Shunichi Shimasaki,Nicholas Ling +1 more
TL;DR: In this paper, six different insulin-like growth factor binding proteins (IGFBPs) have been identified by molecular cloning of their cDNAs from rat and human tissues and designated as IGFBP-1, -2, -3, -4, -5 and -6.
Journal ArticleDOI
Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues
James F. Scott,John K. Cowell,M.E. Robertson,L.M. Priestley,R. B. Wadey,B. Hopkins,Jon Pritchard,Graeme I. Bell,Leslie B. Rall,C. F. Graham,Timothy J. Knott +10 more
TL;DR: In 12 sporadic tumours examined, the expression of the gene coding for insulin-like growth factor-II (IGF-II), localized to the 11p15 region, was markedly increased relative to adult tissues, but was comparable to the level of expression in several fetal tissues including kidney, liver, adrenals and striated muscle.
Related Papers (5)
Insulin-Like Growth Factors and Their Binding Proteins: Biological Actions*
J. I. Jones,David R. Clemmons +1 more