Laminin-111-derived peptides and cancer |
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Authors: | Yamato Kikkawa Kentaro Hozumi Fumihiko Katagiri Motoyoshi Nomizu Hynda K Kleinman Jennifer E Koblinski |
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Institution: | 1Laboratory of Clinical Biochemistry; School of Pharmacy; Tokyo University of Pharmacy and Life Sciences; Tokyo, Japan;2The George Washington School of Medicine; Washington, DC USA;3Women’s Cancer Research Program; Robert H. Lurie Comprehensive Cancer Center; Department of Pathology; Feinberg School of Medicine; Northwestern University; Chicago, IL USA |
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Abstract: | Laminin-111 is a large trimeric basement membrane glycoprotein with many active sites. In particular, four peptides active in tumor malignancy studies have been identified in laminin-111 using a systematic peptide screening method followed by various assays. Two of the peptides (IKVAV and AG73) are found on the α1 chain, one (YIGSR) of the β1 chain and one (C16) on the γ1 chain. The four peptides have distinct activities and receptors. Since three of the peptides (IKVAV, AG73 and C16) strongly promote tumor growth, this may explain the potent effects laminin-111 has on malignant cells. The peptide, YIGSR, decreases tumor growth and experimental metastasis via a 32/67 kD receptor while IKVAV increases tumor growth, angiogenesis and protease activity via integrin receptors. AG73 increases tumor growth and metastases via syndecan receptors. C16 increases tumor growth and angiogenesis via integrins. Identification of such sites on laminin-111 will have use in defining strategies to develop therapeutics for cancer. |
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Keywords: | laminin-111 synthetic peptide metastasis tumor growth angiogenesis migration adhesion basement membrane proteases |
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