Pyke C, Rømer J, Kallunki P, Lund L R, Ralfkiaer E, Danø K, Tryggvason K
Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
Am J Pathol. 1994 Oct;145(4):782-91.
All known laminin isoforms are cross-shaped heterotrimeric molecules, consisting of one heavy alpha chain and two light beta and gamma chains. Recently, a cDNA encoding a new gamma chain from laminin 5 (also known as kalinin) was sequenced. This chain, named gamma 2, showed extended homology to the classical gamma 1 chain but differed from this by lacking the terminal globular domain. Recent data, indicating an important role of the gamma 2 chain gene in establishing adhesion contacts between epithelial cells and basement membranes, prompted us to investigate whether the gamma 2 chain gene is aberrantly expressed in cancer tissue, and if so whether its localization could provide clues to its possible role in cancer dissemination. Routinely processed tissue specimens from 36 cases of human cancer were investigated, including 16 cases of colon adenocarcinoma, 7 ductal mammary carcinomas, 4 squamous cell carcinomas, 3 malignant melanomas and 6 sarcomas. In situ hybridization for the detection of mRNAs for the gamma 2 chain and for the classical laminin chains alpha 1, beta 1, and gamma 1 was performed using S-35 labeled antisense RNA probes. As positive control of the specificity of the gamma 2 chain mRNA detection, two different anti-sense probes derived from two nonoverlapping cDNA clones were used. Malignant cells were found to express the gamma 2 chain in 29 of the 30 carcinomas studied and the expression was particularly high in cancer cells located at the invasion front. In contrast, mesenchymally derived cancer cells in three different types of sarcomas did not express the gamma 2 chain. In colon cancer there was a clear histological correlation between the expression of gamma 2 chain by cancer cells and their engagement in tumor budding processes. Laminin chains alpha 1, beta 1, and gamma 1 were weakly expressed throughout cancerous areas with no apparent correlation to sites of invasion. The aberrant expression of the gamma 2 chain gene seen in invasively growing cancer cells point to a role of this molecule in establishing focal adhesions of cancer cells to the extracellular matrix during their migration through surrounding normal tissue.
所有已知的层粘连蛋白异构体都是十字形的异源三聚体分子，由一条重的α链和两条轻的β链及γ链组成。最近，对编码层粘连蛋白5（也称为卡利宁）中新γ链的cDNA进行了测序。这条链名为γ2，与经典的γ1链具有广泛的同源性，但与之不同的是缺乏末端球状结构域。最近的数据表明γ2链基因在建立上皮细胞与基底膜之间的黏附接触中起重要作用，这促使我们研究γ2链基因在癌组织中是否异常表达，如果是，其定位是否能为其在癌症扩散中可能发挥的作用提供线索。对36例人类癌症的常规处理组织标本进行了研究，包括16例结肠腺癌、7例乳腺导管癌、4例鳞状细胞癌、3例恶性黑色素瘤和6例肉瘤。使用S-35标记的反义RNA探针进行原位杂交，以检测γ2链以及经典层粘连蛋白链α1、β1和γ1的mRNA。作为γ2链mRNA检测特异性的阳性对照，使用了来自两个不重叠cDNA克隆的两种不同反义探针。在所研究的30例癌中的29例中发现恶性细胞表达γ2链，并且在位于侵袭前沿的癌细胞中表达特别高。相反，三种不同类型肉瘤中来源于间充质的癌细胞不表达γ2链。在结肠癌中，癌细胞γ2链的表达与其参与肿瘤芽生过程之间存在明显的组织学相关性。层粘连蛋白链α1、β1和γ1在整个癌区表达较弱，与侵袭部位无明显相关性。侵袭性生长的癌细胞中γ2链基因的异常表达表明该分子在癌细胞通过周围正常组织迁移过程中建立与细胞外基质的粘着斑中起作用。
