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Human relaxin-2: historical perspectives and role in cancer biology

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Abstract

One of the most recognised and studied family of peptide hormones is the insulin superfamily. Within this family is the relaxin subfamily which comprises seven members: relaxin-1, -2 and -3 and insulin-like peptides 3, 4, 5 and 6. Besides exhibiting sequence similarities, each member exists as an active A–B heterodimer linked by three disulfide bonds. This mini-review is divided into three broad themes: an overview of all insulin superfamily members (including structural similarities); roles of each superfamily member and finally, a focus on the pleiotropic peptide hormone, human relaxin-2. In addition to promoting vasodilatory effects leading to evaluation in Phase III clinical trials for the treatment of acute heart failure, relaxin has recently been shown to be highly expressed by cancer cells, aiding in their proliferation, invasiveness and metastasis. These contrary effects of relaxin are discussed together with current efforts in the development of relaxin antagonists that may possess future therapeutic potential for the treatment of certain cancers.

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Acknowledgments

V.B.N. is a recipient of a Melbourne Research Scholarship by the University of Melbourne; C.S.S. is supported by a National Heart Foundation of Australia and National Health and Medical Research Council (NHMRC) of Australia RD Wright Fellowship; M.A.H was the recipient of Reid Trust and Florey Foundation Trust Fellowships and J.D.W is an NHMRC Principal Research Fellow. Some of the authors’ research reported in this review was supported by NHMRC Project Grants 508995 and 1023078. Research at the FNI was supported by the Victorian Government’s Operational Infrastructure Support Program.

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The authors declare that they have no conflict of interest.

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Nair, V.B., Samuel, C.S., Separovic, F. et al. Human relaxin-2: historical perspectives and role in cancer biology. Amino Acids 43, 1131–1140 (2012). https://doi.org/10.1007/s00726-012-1375-y

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