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.
Blase
L
L
Institute of Pathology, University of Heidelberg, Germany.
Daniel
P T
PT
Koretz
K
K
Schwartz-Albiez
R
R
Möller
P
P
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D002051:Burkitt Lymphoma / Q000473:pathology; D002448:Cell Adhesion; D006801:Humans; D016023:Integrins / Q000096:biosynthesis*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation / Q000473:pathology; D017469:Receptors, Fibronectin / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D016023:Integrins; D017469:Receptors, Fibronectin