Nerlich A G, Lebeau A, Hagedorn H G, Sauer U, Schleicher E D
Pathologisches Institut, Universität München, Germany.
Anticancer Res. 1998 Sep-Oct;18(5A):3515-20.
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.
在本研究中，我们比较了乳腺浸润性癌（腺癌）和喉癌（鳞状细胞癌，SCC）中主要基底膜（BM）成分及其mRNA的定位，以确定在生物学行为不同的恶性肿瘤中BM产生和沉积的程度。因此，乳腺癌通常表现出快速的局部区域/全身扩散，而喉SCC通常表现出更局限于局部的生长模式。正常乳腺和喉黏膜显示出完整的上皮BM，这通过对IV型胶原、层粘连蛋白-1、硫酸乙酰肝素蛋白聚糖（基底膜聚糖）和纤连蛋白的连续线性染色得以证明，以及喉黏膜中的VII型胶原也是如此。然而，这种连续染色在浸润性癌中消失了，不过对两种肿瘤类型的影响不同。在乳腺癌中，即使在高分化肿瘤中也能看到各种BM成分的完全缺失，而在SCC中，高分化癌比低分化癌保留了更多的BM物质。在SCC中，VII型胶原的“早期”缺失与IV型胶原、层粘连蛋白、基底膜聚糖和纤连蛋白的“后期”缺失形成对比，但其程度与分化程度降低相关。与蛋白质结果相反，通过原位杂交我们观察到IV型胶原、基底膜聚糖和纤连蛋白的mRNA有显著表达。两种肿瘤类型的结果模式相似，且与肿瘤细胞分化无显著相关性。肿瘤细胞和基质细胞均呈阳性标记，基质细胞的标记更为广泛。我们的观察结果表明，乳腺和喉癌中BM成分的mRNA有类似的上调，但BM蛋白沉积存在显著差异，因此提示可能存在BM蛋白水解的主要差异或进一步的翻译缺陷。此外，可以推测，乳腺癌中BM物质的量远少于喉癌，这可能与这些肿瘤更具侵袭性的转移扩散有关，特别是与SCC相比。
