Metastin: Ligand for G-Protein Coupled Receptor that Suppresses Metastasis- Peptides International

Metastin (Human, 45-54)
A Novel Endogenous Ligand for a G-Protein Coupled Receptor
Which Suppresses Metastasis made by the Peptide
Institute and available from Peptides International

Cancer is currently one of the leading causes of death throughout the world. Strategies for eliminating or controlling cancer have increasingly focussed on metastasis. The multistep mechanism in metastasis involves the disassociation of cancerous cells from malignant tumors and the subsequent invasion and proliferation in surrounding or distant tissues. One endogenous mechanism for cell proliferation involves the product from the gene known as KiSS-1, which has been shown to suppress metastasis of human melanomas and breast carcinomas. Although the exact way in which it suppresses metastasis is not known, it may present a new avenue for treatment. KiSS-1 encodes a 145-amino acid residue peptide, which is further processed to a final 54-amino acid peptide with C-terminal amidation. The final peptide named metastin was found to be the ligand to a G-protein-coupled orphan receptor known as OT7T175 or AXOR12 (K_i = 0.34 nM). Expression of this gene was found to be very high in human placenta and testis followed by the pituitary and spinal cord, with moderate levels in the liver, pancreas and intestines. Although the OT7T175/AXOR12 receptor shares 39.2% sequence homology with human galanin receptor GALR2, it showed no response to galanin and galanin-like peptides. However, a significant increase in intracellular calcium ion concentration was observed with treatment of the CHO cells with human placental extract (1).

Recently new peptides from invertebrate sources have been identified as ligands to the OT7T175/AXOR12 receptor. They all share a C-terminal LRF- or LRW-amide motif and are collectively known as kisspeptins (2,3). This receptor shares 81% homology with the rat orphan receptor GPR54, indicating that they may be orthologs. Activity studies showed that the free acid form of the peptide had very weak affinity, translating into 10,000-fold less activity, but N-terminally truncated (amidated) fragments were found to be three to ten times more active. This indicates the amidated 45-54 fragment is directly involved in the ligand receptor interaction. The expression of the peptide in the different tissues indicates involvement in endocrine function and regulation. This has been confirmed by the stimulation of oxytocin secretion in rats upon treatment with metastin (3). This minimally active fragment is now prepared by the Peptide Institute scientists and is available for further research studies and is not intended for human use.

1. 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, and M. Fujino, Nature, 411, 613 (2001). (Original; Metastin)

2. A.I. Muir, L. Chamberlain, N.A. Elshourbagy, D. Michalovich, D.J. Moore, A. Calamari, P.G. Szekeres, H.M. Sarau, J.K. Chambers, P. Murdock, K. Steplewski, U. Shabon, J.E. Miller, S.E. Middleton, J.G. Darker, C.G.C. Larminie, S. Wilson, D.J. Bergsma,, J. Biol. Chem., 276, 28969 (2001). (Original)

3. M. Kotani, M. Detheux, A. Vandenbogaerde, D. Communi, J.-M. Vanderwinden, E. Le Poul, S. Brezillon, R. Tyldesley, N. Suarez-Huerta, F. Vandeput, C. Blanpain, S. N. Schiffmann, G. Vassart, and M. Parmentier, J. Biol. Chem., in press (Online July 16; epub M104847200). (Original; Kisspeptin)

CODE	PRODUCT DESCRIPTION	VIAL	USD
PMT-4389-v NEW!	Metastin (Human, 45-54) KiSS-1 Gene Product (Human, 112-121 Amide), Kisspeptin-10 Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH₂ (M.W. 1302.4) C₆₃H₈₃N₁₇O₁₄ Endogenous Ligand for G-Protein Coupled Receptor hOT7T175 This compound is distributed through Peptide Institute, Inc. under license of Takeda Chemical Industries, Ltd.	0.5 mg	79

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