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Melanoma-expressed CD70 is involved in invasion and metastasis.

Abstract：

BACKGROUND:CD70 is a costimulatory molecule of the tumour necrosis factor family expressed in activated immune cells and some solid tumours. In lymphocytes CD70 triggers T cell-mediated cytotoxicity and mitogen-activated protein kinase phosphorylation. METHODS:We evaluated the expression of CD70 in biopsies and melanoma cell lines. Using melanoma cell lines positive or not for CD70, we analysed CD70 function on melanoma progression. RESULTS:We report CD70 expression in human melanoma cell lines and tumour cells from melanoma biopsies. This expression was observed in 95% of primary melanomas but only 37% of metastases. Both monomeric and trimeric forms of CD70 were detected in tumour cell membrane fractions, whereas cytoplasmic fractions contained almost exclusively monomeric CD70. In vitro and in vivo experiments demonstrated that CD70 expression inhibited melanoma cell migration, invasion and pulmonary metastasis implantation independently of the tumour immune microenvironment. Increasing the levels of the trimeric form of CD70 through monoclonal antibody binding led to an increase in CD70+ melanoma cell invasiveness through MAPK pathway activation, RhoE overexpression, ROCK1 and MYPT1 phosphorylation decrease, and stress fibres and focal adhesions disappearance. CONCLUSIONS:Our results describe a new non-immunological function of melanoma-expressed CD70, which involves melanoma invasiveness through MAPK pathway, RhoE and cytoskeletal modulation.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Pich C,Sarrabayrouse G,Teiti I,Mariamé B,Rochaix P,Lamant L,Favre G,Maisongrosse V,Tilkin-Mariamé AF

doi

10.1038/bjc.2015.412

subject

Has Abstract

pub_date

2016-01-12 00:00:00

pages

63-70

issue

1

eissn

0007-0920

issn

1532-1827

pii

bjc2015412

journal_volume

114

pub_type

杂志文章

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