Laminin-421 produced by lymphatic endothelial cells induces chemotaxis for human melanoma cells.
Melanoma has a high tendency to metastasize to lymph nodes, which is one of the clinicopathological factors to indicate poor prognosis. Recent investigations have shown the importance of lymphangiogenesis in lymph node metastasis in a variety of human tumors including melanoma. However, molecular mechanism of lymphatic metastasis is still poorly defined. We examined influence of interactions between normal lymphatic endothelial cells (LECs) and melanoma cells on cell migration. Medium conditioned with LEC (LEC-CM) contained chemotactic and chemokinetic activities for human melanoma cell lines. The chemotactic activity was fractionated in more than 100 kDa, and inactivated by heat-treatment. The chemotactic activity of LEC-CM was abolished by immunodepletion with anti-laminin-1 antibody. And immunoprecipitation and Western blot analyses revealed that LEC-CM contained laminin-421. When melanoma C8161 cells were treated with function-blocking antibodies to integrin alpha3 or alpha6, their chemotactic responses to LEC-CM were markedly reduced. Furthermore, the knock-down of tetraspanin CD151 weakened the chemotactic responses of C8161 and MeWo cells to LEC-CM. These data suggest that laminin-421 secreted by LEC possibly facilitates lymphatic metastasis through the induction of chemotaxis of melanoma cells.
Saito
Noriko
N
Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
Hamada
Jun-ichi
J
Furukawa
Hiroshi
H
Tsutsumida
Arata
A
Oyama
Akihiko
A
Funayama
Emi
E
Saito
Akira
A
Tsuji
Tsutomu
T
Tada
Mitsuhiro
M
Moriuchi
Tetsuya
T
Yamamoto
Yuhei
Y
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000737:chemistry; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009361:Neoplasm Invasiveness / Q000473:pathology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D060185:Tetraspanin 24
D015703:Antigens, CD; D015415:Biomarkers; C554715:CD151 protein, human; C554716:Cd151 protein, mouse; D017077:Culture Media, Conditioned; D016023:Integrins; D007797:Laminin; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D060185:Tetraspanin 24