Laminin gamma 1 chain peptide, C-16 (KAFDITYVRLKF), promotes migration, MMP-9 secretion, and pulmonary metastasis of B16-F10 mouse melanoma cells.
Laminin-1, a heterotrimer of alpha 1, beta 1, and gamma 1 chains specific to basement membrane, promotes cell adhesion and migration, proteinase secretion and metastases of tumour cells. Several active sites on the alpha 1 chain have been found to promote B16-F10 melanoma lung colonisation and here we have determined whether additional tumour promoting sites exist on the beta 1 and gamma 1 chains. Recently, we have identified novel cell adhesive peptides derived from laminin beta 1 and gamma 1 chains by systematic screening of synthetic peptides. Nine beta 1 peptides and seven gamma 1 peptides active for cell adhesion were tested for their effects on experimental pulmonary metastases of B16-F10 mouse melanoma cells in vivo. The most active adhesive peptide derived from the gamma 1 chain globular domain, C-16 (KAFDITYVRLKF), significantly enhanced pulmonary metastases of B16-F10 cells, whereas no other peptides showed enhancement. C-16 also stimulated migration of B16-F10 cells in the Boyden chamber assay in vitro. Furthermore, C-16 significantly induced the production of MMP-9 from B16-F10 cells. These results suggest that this specific laminin gamma 1 chain peptide has a metastasis-promoting activity and might be a new molecular target of anti-cancer treatment.
Kuratomi
Y
Y
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, NIH, Bethesda, Maryland, MD 20892, USA. kuratomi@qent.med.jyushu-u.ac.jp
Nomizu
M
M
Tanaka
K
K
Ponce
M L
ML
Komiyama
S
S
Kleinman
H K
HK
Yamada
Y
Y
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects*; D004195:Disease Models, Animal; D007797:Laminin / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000556:secondary* / Q000662:veterinary; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008545:Melanoma / Q000473:pathology* / Q000662:veterinary; D051379:Mice; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007797:Laminin; D010446:Peptide Fragments; C089141:laminin gamma 1; D020780:Matrix Metalloproteinase 9