Cancer Biology

Blocked by a KiSS

Science's STKE  05 Jun 2001:
Vol. 2001, Issue 85, pp. tw1
DOI: 10.1126/stke.2001.85.tw1

Cancers can spread to other tissues through a process called metastasis. Ohtaki et al. isolated and characterized a ligand (metastin) from placenta for the orphan G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) hOT7T175. Metastin is believed to be the product of the KiSS-1, a known metastasis suppressor. Application of metastin or metastin protein fragments promoted an elevation in intracellular Ca2+ concentration in cells transfected to express the orphan GPCR. Application of metastin to hOT7T175-transfected Chinese hamster ovary or B16-BL6 melanoma cells inhibited their migration and chemotaxis toward fetal calf serum; and in the melanoma cells, metastin induced the formation of stress fibers and phosphorylation of focal adhesion kinase and paxillin. Treatment of animals induced to form metastatic tumors through the injection of the transfected B16-BL6 cells showed that metastin decreased the number of metastatic foci. However, metastin did not affect growth of the primary tumor. These results are intriguing and may point to a new direction for inhibiting tumor metastasis, as well as contribute to the identification of a new GPCR and ligand that regulate cell adhesion.

T. Ohtaki, Y. Shintani, S. Honda, H. Matsumoto, A. Hori, K. Kanehashi, Y. Terao, S. Kumano, Y. Takatsu, Y. Masuda, Y. Ishibashi, T. Watanabe, M. Asada, T. Yamada, M. Suenaga, C. Kitada, S. Usuki, T. Kurokawa, H. Onda, O. Nishimura, M. Fujino, Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411, 613-617 (2001). [Online Journal]