Relaxin-Like Peptides in Neoplastic Lesions

Abstract

The two members of the relaxin family of insulin-like peptide hormones, relaxin and INSL3, and their cognate G protein coupled receptors LGR7 and LGR8, respectively, are present in human tumor tissues. Although the physiological role and signal transduction pathways engaged by relaxin-like members in tumor tissues are still largely unknown, novel data mainly obtained from in-vitro cellular models suggest that relaxin-like peptides influence cellular functions associated with motility and migration, cytoskeletal rearrangement and enzyme production and secretion. The expression of relaxin-like peptides appears to be regulated in a tumor-specific context by the actions of various nuclear receptors. This review summarizes most recent findings on the potential functions of relaxin/ INSL3 ligand-receptor systems in tumor tissues and follows an organ-specific approach.

RLN2 and its role in cancer

“…This was the first study to indicate the possible use of a relaxin antagonist to both investigate the progression and course of tumourigenesis as well as it suggest a possible therapeutic agent for use in the treatment of prostate cancer. Relaxin-like peptides and INSL3 have been associated with a number of other tumours (Klonisch et al, 2005) including malignancies in the gastrointestinal tract (Stemmermann et al, 1994) thyroid gland (Homach- Klonisch et al, 2006), colorectum (Alfonso et al, 2005), and the male and female reproductive tracts (Silvertown et al, 2003a) in addition to the report above on relaxin and tumour development in breast and prostate. Although the data are not as fulsome for these other cancers, common themes emerge: there are higher levels of expression of transcripts for relaxin and its receptor in malignant cell forms, and in some cases correlations reported between increased relaxin expression, circulating levels of hormone, tendency to malignancy and incidence of metastasis (Homach- Klonisch et al, 2006).…”

Insulin-like factor 3 gene mutations in testicular dysgenesis syndrome: clinical and functional characterization

“…LGR8 system in testicular cancer has not yet been analysed; however, INSL3 has been implicated in tumorigenesis in other organs (Klonisch et al, 2005). In this study, we tried to clarify the role of INSL3 in human testicular descent and explored the hypothesis that the mutations in INSL3 gene may play a role in the development of TDS.…”