Journal
CLINICAL SCIENCE
Volume 124, Issue 3-4, Pages 215-229Publisher
PORTLAND PRESS LTD
DOI: 10.1042/CS20120343
Keywords
binding protein; cancer; insulin-like growth factor (IGF); insulin-like growth factor-binding protein-6 (IGFBP-6); therapeutic
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Funding
- National Health and Medical Research Council of Australia
- Australian Research Council
- Cancer Council Victoria
- Alfred Research Trust
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The IGF (insulin-like growth factor) system is essential for physiological growth and it is also implicated in a number of diseases including cancer. IGF activity is modulated by a family of high-affinity IGF-binding proteins, and IGFBP-6 is distinctive because of its marked binding preference for IGF-II over IGF-I. A principal role for IGFBP-6 is inhibition of IGF-II actions, but recent studies have indicated that IGFBP-6 also has IGF-independent effects, including inhibition of angiogenesis and promotion of cancer cell migration. The present review briefly summarizes the IGF system in physiology and disease before focusing on recent studies on the regulation and actions of IGFBP-6, and its potential roles in cancer cells. Given the widespread interest in IGF inhibition in cancer therapeutics, increasing our understanding of the mechanisms underlying the actions of the IGF ligands, receptors and binding proteins, including IGFBP-6, will enhance our ability to develop optimal treatments that can be targeted to the most appropriate patients.
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