The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge

Durai, Rajaraman; Yang, Wenxuan; Gupta, Suman Lata; Seifalian, Alexander M.; Winslet, Marc C.

doi:10.1007/s00384-004-0675-4

Cited by 100 publications

(90 citation statements)

References 101 publications

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“…The possible role in promoting oncogenic transformation, growth, and survival of colorectal neoplasm of the insulin-like growth factor (IGF) system, which includes IGF-I, IGF-II, multiple IGF-binding proteins (IGFBP), and IGF type-1 receptors (IGF-IR), has been investigated (1)(2)(3)(4)(5). IGF-IR is a receptor common to both IGF-I and IGF-II, and binding of the receptor to these IGFs causes activation of downstream signaling cascades resulting in proliferative and antiapoptotic effects.…”

Section: Introductionmentioning

confidence: 99%

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Matsunaka

Miyamoto

Shitara

et al. 2010

Molecular Cancer Therapeutics

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Insulin-like growth factors (IGF-I and IGF-II) play important roles in intestinal tumorigenesis. To investigate the effectiveness of IGF-targeting strategies, we conducted an in vivo study using anti-mouse neutralizing antibodies IGF-I (KM3168) and IGF-II (KM1468). Six-and 10-week-old Apc +/− mice were given KM3168 and/or KM1468 i.p. at two doses (0.01 or 0.1 μg/g weight) once or twice weekly for 4 weeks. To clarify the source of IGFs in vivo, we evaluated the expression levels of IGFs in the liver, normal small intestine, and polyps of the small intestine of Apc +/− mice. The phosphorylation status of IGF signalrelated molecules was examined using immunostaining to understand the mechanism underlying the effects of IGF-neutralizing antibody. The plasma half-life was 168 for KM3168 and 85 hours for KM1468. In two lineages of Apc +/− mice (Apc 1309 and Apc Min/+ ), a low dose (0.01 μg/g weight) of KM3168 and KM1468 significantly reduced the number of polyps when given once and twice weekly, respectively. Combined administration of the effective dose of each antibody had an additive effect. The liver was the main source of IGF-I, whereas the polyps of the small intestine and normal small intestine were the main source of IGF-II. IGF-neutralizing antibodies decreased the phosphorylation of IGF type 1 receptor and inhibited the signal transduction of the Akt pathway. These results suggest that IGF-I and IGF-II play important roles in polyp formation in Apc +/− mice and that specific antibodies to IGF-I and IGF-II may be promising antitumor agents. Mol Cancer Ther; 9(2); 419-28. ©2010 AACR.

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Section: Introductionmentioning

confidence: 99%

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Matsunaka

Miyamoto

Shitara

et al. 2010

Molecular Cancer Therapeutics

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“…In combination with other growth factors and steroids, they neutralise the effect of antiproliferative molecules on cancer growth, thus contributing to metastatic events (Bahr and Groner, 2005). Moreover, epidemiological studies have unambiguously correlated high levels of circulating IGF-I with prostate, breast, colorectal and lung cancers (Holly, 2004;LeRoith and Helman, 2004;Durai et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…IGFBPs modulate IGF transport and IGFR binding, dramatically slowing down IGF clearance, but also hindering their mitogenic activity (Burger et al, 2005). Among these proteins, IGFBP-2 and -6 have a higher affinity for IGF-II than for IGF-I, while IGFBP-1, -3, -4 and -5 prefer IGF-I over IGF-II (Durai et al, 2005) and none of them binds insulin. IGFBP-3 is the most abundant of the IGFBPs and accounts for more than 90% of IGF binding.…”

Section: Introductionmentioning

confidence: 99%

“…It is the only IGFBP that recruits an additional element, an 80-kDa liver-derived growthhormone-regulated glycoprotein termed the acid-labile subunit, as a third binding partner to produce a ternary complex that cannot traverse the capillary. In this way, IGFBP-3-bound IGF is kept within the vascular system (Durai et al, 2005). In the aggregate to IGF-binding, a number of IGF-independent functions have been described for IGFBPs, many of which occur through interaction with extracellular matrix (ECM) components (Miyakoshi et al, 2001;Bach et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease

Tallant

García‐Castellanos

Marrero

et al. 2007

BCHM

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Human growth and development are conditioned by insulin-like growth factors (IGFs), which have also implications in pathology. Most IGF molecules are sequestered by IGF-binding proteins (IGFBPs) so that exertion of IGF activity requires disturbance of these complexes. This is achieved by proteolysis mediated by IGFBP proteases, among which the best characterised is human PAPP-A, the first member of the pappalysin family of metzincins. We have previously identified and studied the only archaeal homologue found to date, Methanosarcina acetivorans ulilysin. This is a proteolytically functional enzyme encompassing a pappalysin catalytic domain and a pro-domain involved in maintenance of latency of the zymogen, proulilysin. Once activated, the protein hydrolyses IGFBP-2 to -6 and insulin chain b in vitro. We report here that ulilysin is also active against several other substrates, viz (azo)casein, azoalbumin, and extracellular matrix components. Ulilysin has gelatinolytic but not collagenolytic activity. Moreover, the proteolysis-resistant skeletal proteins actin and elastin are also cleaved, as is fibrinogen, but not plasmin and a1-antitrypsin from the blood coagulation cascade. Ulilysin develops optimal activity at pH 7.5 and strictly requires peptide bonds preceding an arginine residue, as determined by means of a novel fluorescence resonance energy transfer assay, thus pointing to biotechnological applications as an enzyme complementary to trypsin.These two authors contributed equally to this work. a

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“…Increased levels of IGF ligands and/or over-expression of IGF receptor have been observed in many cancers and have been shown to affect proliferation, differentiation, migration and apoptosis of cancer cells [1,3].…”

Section: Igf System and Colorectal Cancer: Emerging Evidencementioning

confidence: 99%

Role of insulin-like growth factor-1R system in colorectal carcinogenesis

Donovan

Kummar

2008

Critical Reviews in Oncology/Hematology

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The insulin-like growth factor (IGF) system is comprised of receptors, ligands (IGF-I and IGF-II), and a family of binding proteins (IGFBPs). It plays an important role in growth and development and in the maintenance of normal homeostasis. We present a review of the current laboratory and epidemiologic evidence that suggests an important role of the IGF system in colorectal carcinogenesis. Due to the complexity of this system, we have focused the review on the role of the IGF-1 receptor and its ligands in colorectal carcinogenesis and the strategies to block this pathway as a potential anti-cancer therapy.

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The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge

Cited by 100 publications

References 101 publications

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Ligand-Specific Antibodies to Insulin-Like Growth Factors Suppress Intestinal Polyp Formation in Apc+/− Mice

Activity of ulilysin, an archaeal PAPP-A-related gelatinase and IGFBP protease

Role of insulin-like growth factor-1R system in colorectal carcinogenesis

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