A Subset of Host B Lymphocytes Controls Melanoma Metastasis through a Melanoma Cell Adhesion Molecule/MUC18-Dependent Interaction: Evidence from Mice and Humans

A Subset of Host B Lymphocytes Controls Melanoma Metastasis through a Melanoma Cell Adhesion Molecule/MUC18-Dependent Interaction: Evidence from Mice and Humans

Autor Staquicini, Fernanda I. Google Scholar
Tandle, Anita Google Scholar
Libutti, Steven K. Google Scholar
Sun, Jessica Google Scholar
Zigler, Maya Google Scholar
Bar-Eli, Menashe Google Scholar
Aliperti, Fabiana Autor UNIFESP Google Scholar
Perez, Elizabeth C. Autor UNIFESP Google Scholar
Gershenwald, Jeffrey E. Google Scholar
Mariano, Mario Autor UNIFESP Google Scholar
Pasqualini, Renata Google Scholar
Arap, Wadih Google Scholar
Lopes, Jose Daniel Autor UNIFESP Google Scholar
Instituição Univ Texas MD Anderson Canc Ctr
NCI
Universidade Federal de São Paulo (UNIFESP)
Resumo Host immunity affects tumor metastasis but the corresponding cellular and molecular mechanisms are not entirely clear. Here, we show that a subset of B lymphocytes (termed B-1 population), but not other lymphocytes, has prometastatic effects on melanoma cells in vivo through a direct heterotypic cell-cell interaction. in the classic B16 mouse melanoma model, one mechanism underlying this phenomenon is a specific up-regulation and subsequent homophilic interaction mediated by the cell surface glycoprotein MUC18 (also known as melanoma cell adhesion molecule). Presence of B-1 lymphocytes in a panel of tumor samples from melanoma patients directly correlates with MUC18 expression in melanoma cells, indicating that the same protein interaction exists in humans. These results suggest a new but as yet unrecognized functional role for host B-1 lymphocytes in tumor metastasis and establish a biochemical basis for such observations. Our findings support the counterintuitive central hypothesis in which a primitive layer of the immune system actually contributes to tumor progression and metastasis in a mouse model and in melanoma patients. Given that monoclonal antibodies against MUC18 are in preclinical development but the reason for their antitumor activity is not well understood, these translational results are relevant in the setting of human melanoma and perhaps of other cancers. [Cancer Res 2008;68(20):8419-28]
Idioma Inglês
Financiador Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Department of Defense
NCI
Gillson-Longenbaugh Foundation
AngelWorks
Data de publicação 2008-10-15
Publicado em Cancer Research. Philadelphia: Amer Assoc Cancer Research, v. 68, n. 20, p. 8419-8428, 2008.
ISSN 0008-5472 (Sherpa/Romeo, fator de impacto)
Publicador Amer Assoc Cancer Research
Extensão 8419-8428
Fonte http://dx.doi.org/10.1158/0008-5472.CAN-08-1242
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000260323400027
Endereço permanente http://repositorio.unifesp.br/handle/11600/30968

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