The Role of the IGF System in Cancer: From Basic to Clinical Studies and Clinical Applications

Abstract

Insulin-like growth factors (IGFs) are important mediators of growth, development, and survival, are synthesized by almost any tissue in the body, and their action is modulated by a complex network of molecules, including binding proteins, proteases and receptors, which all comprise the IGF system. Evidence from in vitro and animal studies suggests that overexpression of IGFs by cancer cells and/or the nearby stroma as well as the type IGF-I receptor by the cancer cells may play a significant role in establishing a transformed phenotype in an increasing number of malignancies. More specifically, IGFs may promote cell cycle progression and inhibition of apoptosis either by directly associating with other growth factors or indirectly by interacting with other molecular systems which have an established role in carcinogenesis and cancer promotion, such as the steroid hormones and integrins. In addition, a growing number of epidemiologic studies suggest that increased serum levels of IGFs and/or altered levels of their binding proteins are associated with increased risk for developing several malignancies. These data indicate that IGF dysregulation should now be considered as an important independent factor for cancer risk, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.

Relationship between a wide range of alcohol consumptions, components of the insulin-like growth factor system and adiponectin

“…As these results may have a potential impact on the prevention of several chronic diseases (Moschos and Mantzoros, 2002;Dal Maso et al, 2004a;Maskarinec et al, 2005), additional large-scale population based studies are needed.…”

“…Only limited information is available on the biological mechanisms and interactions between IGF components, adiponectin and other cancer risk factors (e.g., alcohol) involved in insulin stimulation and energy metabolism (Röjdmark et al, 2000;Yu and Rohan, 2000;Moschos and Mantzoros, 2002;Pollak et al, 2004;Sierksma et al, 2004).…”

ST7-mediated suppression of tumorigenicity of prostate cancer cells is characterized by remodeling of the extracellular matrix

“…Overexpression of the IGF pathway may play a role in several malignancies (Moschos and Mantzoros, 2002). There is strong evidence for the involvement of IGFBP-5 in the progression of intestinal epithelial cells to cancer in the APC Min/À mouse model.…”

The GH–IGF-I axis and breast cancer

“…The study supported the hypothesis that endogenous hormones affect density of mammograms in premenopausal women, in particular showing a positive association with oestrogen levels and mammogram density 64 . High serum concentrations of IGF-1 are associated with an increased risk of breast, prostate, colorectal and lung cancers 65 . In patients with acromegaly, high concentrations of growth hormone stimulate production of high concentrations of IGF-1 and this has been associated with an increased risk of colorectal and breast cancer 66,67 .…”