M. Morini et al., The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity, INT J CANC, 87(3), 2000, pp. 336-342
The alpha 3 beta 1 integrin is elevated in several types of metastatic tumo
r and has been associated with increased migration and invasion. Our analys
is of a series of mammary carcinomas of different histotypes and their corr
esponding metastases demonstrated significantly increased expression of alp
ha 3 beta 1 I in the tumor metastases. We therefore studied alpha 3 beta 1
expression of several human breast carcinoma cell lines and its association
with the invasive phenotype. The MDA-MB-231 cell line expressed high level
s of the beta 1, alpha 2, alpha 3, alpha 5, and alpha 6 integrin subunits a
long with moderate levels of the alpha v beta 3 integrin, This line was hig
hly migratory and the most invasive using a chemo-invasion assay. In contra
st, the other lines tested, MDA-MB-145, MCF-7, and SK-BR-3, showed lower mi
gratory and invasive activity and reduced alpha 3 integrin subunit expressi
on. Metalloproteases capable of degrading collagen IV are necessary for the
invasive process. RT-PCR showed that MDA-MB-231 cells expressed MMP-9, but
not MMP-2, gelatinase/collagenase IV. Gelatin zymography demonstrated that
invading MDA-MB-231 cells released high levels of MMP-9 gelatinase activit
y. A direct role for this gelatinase in MDA-MB-231 cell invasion was confir
med by inhibition of invasion using the metalloprotease inhibitor Batimasta
t. Treatment of MDA-MB-231 cells with a function-blocking anti-alpha 3 anti
body strongly inhibited migration and invasion. This correlated with a mark
ed reduction in MMP-9 activity produced by MDA-MB-231 cells, suggesting a r
ole for alpha 3 beta 1 ligand binding in cell signaling and regulation of e
xtracellular matrix degradation. Int. J. Cancer 87:336-342, 2000. (C) 2000
Wiley-Liss, Inc.