Relaxin‐like peptides in cancer

Abstract The members of the relaxin‐like hormone family, relaxin and INSL3, also known as relaxin‐like factor (RLF) or Leydig cell‐derived insulin‐like factor (LEY‐I‐L), are implicated in various mechanisms associated with tumor cell growth, differentiation, invasion and neovascularization. The recent discovery of the relaxin receptor LGR7 and the INSL3/relaxin receptor LGR8 has provided evidence of an auto/paracrine relaxin‐like action in tumor tissues and enables the elucidation of the cellular pathways involved in the proposed functions of relaxin in tumor biology. Our review summarizes our current knowledge of the expression of relaxin and INSL3 in human neoplastic tissues and discusses the etiological roles of these heterodimeric peptide hormones in cancer. Discussion of possible cellular cascades involved in actions linking relaxin‐like peptides and neoplasia include the role of relaxin‐like peptides in tumor cell growth and differentiation; the effect of relaxin in stimulating the synthesis of the vasodilatory and tumor cell cytostatic and antiapoptotic molecule, nitric oxide; the potential ability of relaxin to upregulate vascular endothelial growth factor to promote angiogenesis and neovascularization and the concerted fine‐tuned action of relaxin on the matrix metalloproteinases on the extracellular matrix to facilitate tumor cell attachment, migration and invasion. © 2003 Wiley‐Liss, Inc.