THE CAPACITY OF HUMAN-MALIGNANT B-LYMPHOCYTES TO DISSEMINATE IN SCID MICE IS CORRELATED WITH FUNCTIONAL EXPRESSION OF THE FIBRONECTIN RECEPTOR ALPHA(5)BETA(1) (CD49E/CD29)

The alpha(5) beta(1) integrin (CD49e/CD29), a heterodimeric membrane protein, is the ''classical'' fibronectin receptor on many cell types. During B-cell ontogeny, expression of the alpha(5)-subunit is developmentally regulated. The alpha(5) beta(1) is decisive for migration on fibronectin substrate and very likely cooperates with other adhesion molecules in transvascular trafficking. To test whether alpha(5) beta(1) influences local growth vs. disseminative spread of neoplastic B-cells in vivo human B-cell lines mimicking different maturational stages were transferred s.c. into severe combined immunodeficiency (SCID) mice and examined for alpha(5) beta(1) expression and for adherence on fibronectin substrate in vitro and ex vivo. All cell lines were locally tumorigenic. Dissemination was observed in all animals carrying Nalm-6 tumors, in one animal with a BL 60 and in 2 mice carrying a Raji tumor. By contrast, Daudi, BJAB and U266 tumors did not disseminate. As evidenced by immunohistochemistry and flow cytometry, all lines and their tumors were to various extents beta(1)-positive but showed considerable differences in alpha(5) expression. The functional surface expression of alpha(5) beta(1) correlated with fibronectin adherence of the lines. Daudi expressed alpha(5) beta(1) in a non-functional configuration which was rendered functional only upon applying high concentrations of Mg++ and Mn++. B-cell lines functionally expressing alpha(5) beta(1) at high or moderate levels disseminated in SCID mice while alpha(5)-negative lines and Daudi did not. These results support the conclusion drawn from an earlier in situ analysis of human B-cell lymphomas/leukemias that the alpha(5) beta(1) integrin contributes to the disseminative phenotype of malignant B cells. (C) 1995 Wiley-Liss, Inc.