The capacity of human malignant B‐lymphocytes to disseminate in scid mice is correlated with functional expression of the fibronectin receptor α5β1 (CD49E/CD29)

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Abstract
The α5β integrin (CD49e/CD29), a heterodimeric membrane protein, is the “classical” fibronectin receptor on many cell types. During B-cell ontogeny, expression of the α5-subunit is developmentally regulated. The αβ1 is decisive for migration on fibronectin substrate and very likely cooperates with other adhesion molecules in transvascular trafficking. To test whether α5β 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 α5β 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 β1-positive but showed considerable differences in α5 expression. The functional surface expression of α5β1correlated with fibronectin adherence of the lines. Daudi expressed α5β1 in a non-functional configuration which was rendered functional only upon applying high concentrations of Mg++ and Mn++. B-cell lines functionally expressing α5β1 at high or moderate levels disseminated in SCID mice while α5-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 α5β1 integrin contributes to the disseminative phenotype of malignant B cells.
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