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From the Institute of Clinical Chemistry and Laboratory
Medicine,*
the Center of Gynecology and
Obstetrics,
and the Department of
Experimental Tumor Biology,§
University of
Münster, Münster, and the Institute of
Immunology,
University of Witten/Herdecke,
Witten, Germany
Overexpression of the c-erbB-2 gene-encoded
p185c-erbB-2 is correlated with early onset of
metastasis in breast cancer patients. Furthermore, the
detection of blood-borne epithelium-derived clustered cells expressing
p185c-erbB-2 was related to advanced stages in breast
cancer. To further elucidate the receptor's function in the metastatic
process of human breast cancers, we analyzed disaggregated
cells and cell clusters from freshly dissected breast cancer tissues.
We studied whether their capability of extravasation is correlated with
their expression of c-erbB-2. A model for the venular
wall was constructed by growing human umbilical vein endothelial cells
(HUVECs) on porous membranes coated with basement membrane
extracellular matrix. In four control breast cancer cell lines
(SK-BR-3, MCF-7, MDA-MB-468, and
MDA-MB-468, the latter transfected with a full-length
c-erbB-2 cDNA vector) producing different levels of the
c-erbB-2 receptor, the expression level
correlated positively with the invasiveness of the cells. The
invasive, predominantly clustered cells from 14 of 23 tumors
were positively stained for p185c-erbB-2 by
immunocytochemistry. Furthermore, we show that the invasive
cell populations express the metastasis-associated proteins matrix
metalloproteinase MMP-2, CD44, and integrins 
vß3
and 6. In this first study on the behavior of cells and cell
clusters from disaggregated operated cancers in an extravasation
model, we could demonstrate the presence of
c-erbB-2-expressing cell subpopulations within the
individual breast cancers that are presumably of high metastatic
potential.
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