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Transformation-associated alterations in interactions between pre-B cells
and fibronectin
FM Lemoine, S Dedhar, GM Lima and CJ Eaves
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Marrow stromal elements produce as yet uncharacterized soluble growth
factors that can stimulate the proliferation of murine pre-B cells,
although close contact between these two cell types appears to ensure a
better pre-B cell response. We have now shown that freshly isolated normal
pre-B cells (ie, the B220+, surface mu- fraction of adult mouse bone
marrow) adhere to fibronectin (FN) via an RGD cell-attachment site, as
shown in a serum-free adherence assay, and they lose this functional
ability on differentiation in vivo into B cells (ie, the B220+, surface mu+
fraction). Similarly, cells from an immortalized but stromal cell-dependent
and nontumorigenic murine pre-B cell line originally derived from a
Whitlock-Witte culture were also found to adhere to fibronectin (FN) via an
RGD cell-attachment site. Moreover, in the presence of anti-FN receptor
antibodies, the ability of this immortalized pre-B cell line to proliferate
when co-cultured with a supportive stromal cell line (M2-10B4 cells) was
markedly reduced (down to 30% of control). This suggests that pre-B cell
attachment to FN on stromal cells may be an important component of the
mechanism by which stromal cells stimulate normal pre-B cell proliferation
and one that is no longer operative to control their more differentiated
progeny. Two differently transformed pre-B cell lines, both of which are
autocrine, stromal-independent, tumorigenic in vivo, and partially or
completely differentiation-arrested at a very early stage of pre-B cell
development, did not bind to FN. In addition, anti-FN receptor antibodies
were much less effective in diminishing the ability of these tumorigenic
pre-B cells to respond to M2-10B4 cell stimulation, which could still be
demonstrated when the tumorigenic pre-B cells were co- cultured with
M2-10B4 cells at a sufficiently low cell density. Analysis of cell surface
molecules immunoprecipitated from both the nontumorigenic and tumorigenic
pre-B cell lines by an anti-FN receptor antibody showed an increase in very
late antigen (VLA) alpha chain(s) in both tumorigenic pre-B cell lines and
a decrease in the beta 1 chain in one. Interestingly, all of the pre-B cell
lines expressed similar amounts of messenger RNA for the beta 1 chain of
the FN receptor. These results suggest that alteration of FN receptor
expression on pre-B cells may represent a mechanism contributing to the
outgrowth of leukemic pre-B cells with an autocrine phenotype and capable
of stromal cell-independent, autonomous growth.
Volume 76,
Issue 11,
pp. 2311-2320,
12/01/1990
Copyright © 1990 by The American Society of Hematology
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