Morphological aspects of altered basement membrane metabolism in invasive carcinomas of the breast and the larynx.
In the present study we compared the localization of major basement membrane (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 usually show a rapid locoregional/systemic spread, while the laryngeal SCCs normally show a more locally restricted growth pattern. While normal mammary glands and laryngeal mucosa revealed an intact epithelial BM as evidenced by a continuous linear staining for collagen IV, laminin-1, heparan sulfate proteoglycan (perlecan) and fibronectin-as well as collagen VII in the larynx mucosa-, this continuous staining was lost in the invasive carcinomas, however, affecting the two tumor types differently. In the breast carcinomas, a complete loss was seen even in well differentiated tumors affecting the various BM components similarly, while in the SCCs well differentiated carcinomas had retained significantly more BM material than poorly differentiated ones. In the SCCs, an "early" loss of collagen VII contrasted with a "later" loss of collagen IV, laminin, perlecan and fibronectin the extent of which was, however, associated with a decreasing degree of differentiation. In contrast to the protein findings, by use of the in-situ hybridization we observed a significant expression of mRNA for collagen IV, perlecan and fibronectin. The resulting pattern was comparable between both tumor types and not significantly related to the tumor cell differentiation. Both tumor cells and stroma cells were positively labelled with a more extensive labelling of the stroma cells. Our observations indicate a similar upregulation of the mRNAs for BM-components in breast and larynx carcinomas, but significant differences in the BM-protein deposition so that either major differences in presumed BM-proteolysis or further translational defects are suggested. Furthermore, it can be speculated that the far lesser amount of BM-material in the breast carcinomas may be linked to the more aggressive metastatic spread of those tumors, particularly when compared to the SCCs.
Nerlich
A G
AG
Pathologisches Institut, Universität München, Germany. Andreas.Nerlich@lrz.uni-muenchen.de
Lebeau
A
A
Hagedorn
H G
HG
Sauer
U
U
Schleicher
E D
ED
D001485:Basement Membrane / Q000737:chemistry / Q000473:pathology; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D003094:Collagen / Q000032:analysis; D005260:Female; D005353:Fibronectins / Q000032:analysis; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000032:analysis; D006801:Humans; D007797:Laminin / Q000032:analysis; D007822:Laryngeal Neoplasms / Q000737:chemistry* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis
D003094:Collagen; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C071927:perlecan