Thus, in addition to its direct, growth stimulatory effect on transformed cells, IGF-I induces the expression of VEGF which can promote the progression of cancer by regulating the development of new blood vessels.
Expression of IGF-1 and IGF-2 in tumor tissues but not in cancer cell cultures indicates an IGF expression located predominantly in stromal parts of cancer tissues.
The debate about a direct or indirect effect of GH and IGF-I on the recurrence of malignancy, especially in the case of rhGH therapy in patients with leukemia, is still going on.
If our observations can be confirmed in larger studies, the findings will provide further evidence to support the role of IGF-I in breast cancer and the link between genetic polymorphism and cancer susceptibility.
Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1R contributes to cancer progression.
In view of the effects of insulin-like growth factor I (IGF-I) on mammary gland development and cancer, we developed a model using MCF-7 human breast cancer cells in which the process of cell separation can be induced by IGF-I.
Clinical trials in patients with acromegaly show GHR blockade to be an exciting new mode of therapy for this condition, and pegvisomant may have a therapeutic role in diseases, such as diabetes and malignancy, in which abnormalities of the GH/IGF-I axis have been observed.
Towards understanding the IGF system during cancer growth and progression, progressive prostate cancer models, such as SV40 large T antigen immortalized human prostate epithelial cells (P69, M2182, M2205, and M12) and LNCaP sublines (C4, C4-2, and C4-2B4), were used.
In rodents, caloric restriction decreases the levels of plasma glucose and insulin-like growth factor I (IGF-1) and postpones or attenuates cancer, immunosenescence, and inflammation without irreversible side effects.
Moreover, there was a good correlation between the expression of IGF-I and IGF-IR in women without cancer: this link was still present in breast tissue from patients with diabetes and cancer, whereas it was lost in patients without diabetes but with cancer.
To further understand the role of the type I insulin-like growth factor (IGF) receptor (IGF1R) in cancer metastasis we inhibited signaling via IGF1R using a C-terminal-truncated IGF1R.
This review presents a model integrating nutrition, insulin and IGF-1 physiology ("bioactive" IGF-1), and carcinogenesis based on the following: (1) insulin and the IGF-1 axis function in an integrated fashion to promote cell growth and survival; (2) chronic exposure to these growth properties enhances carcinogenesis; (3) factors that influence bioactive IGF-1 will affect cancer risk.
Controlling for smoking history and IGFBP-3 strengthened associations with cancer for both IGF-I (OR = 3.00; 95% CI = 1.50-6.01; p(trend) 0.005) and IGF-II (OR = 2.02; 95% CI = 1.07-3.84; p(trend) = 0.04) Associations between the IGFs and cancer risk were stronger for advanced cases.
The receptor for the type 1 insulin-like growth factor (IGF-IR) was identified as a major regulator of the malignant phenotype and a target for cancer therapy.
Pharmacological inhibition and genetic modification of KCC activity demonstrate that KCC is necessary for IGF-1-induced cancer cell invasiveness and proliferation.
The present study shows that physiological stimulation of the GHRH-GH-IGF-I axis in mice with cancer does not promote tumor growth and may provide a viable treatment for cancer cachexia in humans.
The overall goal is to reinforce the need for more complete understanding of the mechanisms of signaling and action of GH and IGF-I, in order to separate, if possible, the potentially beneficial outcomes on growth and on tissue maintenance and repair from deleterious effects on cancer risk and lifespan.
Studies using genetic models of cancer that have been interbred with mice with abnormal levels of IGF-1 will enable the examination of combined effects of energy balance and genetic alterations on the cancer process.
Two STRs, one trinucleotide repeats in the androgen receptor (AR) gene and one dinucleotide repeats in the insulin-like growth factor-I (IGF-I) gene, have been studied for their role in cancer, and the results are conflicting.
Together with studies on nutrient regulation of growth and ageing in the nematode Caenorhabditis elegans, evidence from these model organisms has moved the Insulin/IGF (IIS) and the Target Rapamycin (TOR) signalling pathway onto the centre stage of cellular growth control and made them attractive novel targets for cancer therapy.