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Title: A Subset of Host B Lymphocytes Controls Melanoma Metastasis through a Melanoma Cell Adhesion Molecule/MUC18-Dependent Interaction: Evidence from Mice and Humans
Authors: Staquicini, Fernanda I.
Tandle, Anita
Libutti, Steven K.
Sun, Jessica
Zigler, Maya
Bar-Eli, Menashe
Aliperti, Fabiana [UNIFESP]
Perez, Elizabeth C. [UNIFESP]
Gershenwald, Jeffrey E.
Mariano, Mario [UNIFESP]
Pasqualini, Renata
Arap, Wadih
Lopes, Jose Daniel [UNIFESP]
Univ Texas MD Anderson Canc Ctr
Universidade Federal de São Paulo (UNIFESP)
Issue Date: 15-Oct-2008
Publisher: Amer Assoc Cancer Research
Citation: Cancer Research. Philadelphia: Amer Assoc Cancer Research, v. 68, n. 20, p. 8419-8428, 2008.
Abstract: 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]
ISSN: 0008-5472
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