Ag. Nerlich et al., Morphological aspects of altered basement membrane metabolism in invasive carcinomas of the breast and the larynx, ANTICANC R, 18(5A), 1998, pp. 3515-3520
In the present study we compared the localization of major basement membran
e (BM) components and their mRNAs between invasive carcinomas of the breast
(adenocarcinomas) and larynx carcinomas (squamous cell carcinomas, SCC) in
order to determine the extent of BM production and deposition in malignant
tumors of biologically different behaviour. Thus, breast carcinomas usuall
y show a rapid locoregional/systemic spread, while the laryngeal SCCs norma
lly show a more locally restricted growth pattern. While normal mammary gla
nds and laryngeal mucosa revealed an intact epithelial BM as evidenced by a
continous linear staining for collagen IV, laminin-l, heparan sulfate prot
eoglycan (perlecan) and fibronectin -as well as collagen VII in the larynx
mucosa -, this continuous staining was lost in the invasive carcinomas, how
ever, affecting the two tumor types differently. In the breast carcinomas,
a complete loss was seen even in well differentiated tumors affecting the v
arious BM components similarly, while in the SCCs well differentiated carci
nomas had retained significantly more BM material than poorly differentiate
d ones. In the SCCs, an "early" loss of collagen VII contrasted with a "lat
er" loss of collagen IV, laminin, perlecan and fibronectin the extent of wh
ich was, however, associated with a decreasing degree of differentiation. I
n contrast to the protein findings, by use of the in-situ hybridization we
observed a significant expression of mRNA for collagen IV, perlecan and fib
ronectin. The resulting pattern was comparable between both tumor types and
not significantly related to the tumor cell differentiation. Both tumor ce
lls and stroma cells were positively labelled with a more extensive labelli
ng of the stroma cells. Our observations indicate a similar upregulation of
the mRNAs for BM-components in breast and larynx carcinomas, but significa
nt differences in the BM-protein deposition so that either major difference
s in presumed BM-proteolysis or further translational defects are suggested
. Furthermore, it can be speculated that the far lesser amount of BM-materi
al in the breast carcinomas may be linked to the more aggressive metastatic
spread of those tumors, particularly when compared to the SCCs.