Abstract
Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells. To metastasize, tumor cells must invade or migrate from the primary tumor and be transported to close or distant secondary sites. A tumor cell should successfully accomplish each step of the pathway or metastasis may not develop. KiSS-1 is a human metastasis suppressor gene that inhibits metastasis of human melanomas and breast carcinomas without affecting tumorigenicity. KiSS-1 encodes a carboxy-terminally amidated peptide with 54 amino-acid residues. The peptide was isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor and termed 'metastin'. The literature reports metastin related to human carcinoma, such as melanoma, thyroid cancer, esophageal squamous cell carcinoma (ESCC), hepatocellular carcinoma, pancreatic carcinoma, as well as breast, ovarian, bladder and kidney cancer. These malignancies are difficult to treat and, even in early-stage cancer, a number of patients develop metastasis shortly after surgery. Studies have suggested that metastin inhibits tumor invasion or migration through focal adhesion kinase, paxillin, MAP kinase or Rho A. Additionally, metastin may be a biomarker in ESCC, pancreatic carcinoma and bladder cancer. Metastin has potential as a suitable biomarker in the identification of tumors with high metastatic potential and as a novel effective treatment modality for patients with metastasis.
Highlights
Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells
Ohtaki et al found a rat orphan receptor that was nearly identical to GPR54 during a search for novel G-protein-coupled receptors (GPCRs) using a degenerate polymerase chain reaction (PCR) strategy
Nicolle et al analyzed the expression of metastin and metastin receptor mRNA levels in urothelial carcinoma (UC) using real-time RT-PCR [12]
Summary
Cancer metastasis is a leading cause of death in cancer patients and is a multistep process involving complex interactions between tumor and host cells. Ohtaki et al reported that metastin inhibits the chemotaxis and invasion of metastin receptor-transfected CHO cells in vitro and attenuates the pulmonary metastasis of metastin receptortransfected B16-BL6 melanomas in vivo [2]. A thyroid cancer cell line (ARO) that expresses a metastin receptor was analyzed in order to evaluate the signaling pathways activated by endogenous metastin receptors.
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