Endocrine Abstracts

The heterodimeric peptide hormone relaxin is involved in extracellular matrix turnover during development and lactational differentiation of the breast. Relaxin expression is increased in human breast cancer and serum relaxin levels in breast cancer patients were reported to correlate with metastatic disease. We have established relaxin over-expressing transfectants of the highly invasive estrogen receptor-negative human breast cancer cell line MDA-MB-231 (MDA/RLN) to investigate the role of relaxin in estrogen-independent breast cancer cells. MDA/RLN revealed decreased cellular motility and migration through extracellular matrices when compared to MDA/EGFP control transfectants. S100A4 (metastasin) increased cell motility in different cell models and has been associated with tumor invasiveness. In the present study, we showed that the calcium binding protein S100A4 is down-regulated in stable MDA/RLN transfectants and in paternal MDA-MB-231 breast cancer cells after exposure to human recombinant relaxin. Furthermore, tumor growth in nude mice was studied following subcutaneous injection of MDA/RLN and MDA/EGFP clones and revealed reduced tumor growth of the MDA/RLN xenografts. MDA/RLN xenografts also revealed a down-regulation of S100A4 transcripts and protein. S100A4 siRNA knock-down revealed reduced cell motility suggesting S100A4 to be a downstream target of relaxin/ relaxin receptor signaling. (Supported by Wilhelm-Roux-Program, FKZ 15/09)