Collagenase-3 (MMP-13) is expressed by tumor cells in invasive vulvar squamous cell carcinomas
Collagenase-3 (MMP-13) is expressed by tumor cells in invasive vulvar squamous cell carcinomas
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DOI：
10.1016/s0002-9440(10)65293-5
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发表时间：
1999-02-01
影响因子：
6
通讯作者：
Kähäri, VM
中科院分区：
文献类型：
--
作者：
Johansson, N;Vaalamo, M;Kähäri, VM
胶原酶-3（MMP-13）是一种人基质金属蛋白酶，在头颈部鳞状细胞癌（SCC）的侵袭性肿瘤细胞中特异性表达。在此，我们通过检测MMP-13在女性生殖道侵袭性恶性肿瘤中的表达，进一步阐明了MMP-13在肿瘤侵袭中的作用。采用原位杂交，MMP-13 mRNA的表达检测在9 12外阴SCC，主要是在肿瘤细胞，但不是在完整的外阴上皮，在宫颈SCC（n = 12），或在子宫内膜（n = 11）或卵巢腺癌（n = 8）。MMP-13的表达尤其丰富的外阴癌淋巴结转移，并与表达的膜型1 MMP的肿瘤细胞和明胶酶-IL（MMP-2）的基质细胞，通过免疫组化检测。MMP-13 mRNA在11株外阴癌细胞系中有9株表达，在6株宫颈癌细胞系中有4株表达，而在子宫内膜癌（n = 10）和卵巢癌（n = 9）细胞系中均为阴性。MMP-13的表达与p53基因突变之间无相关性。然而，在6种携带HPV 16或68 DNA的外阴和宫颈SCC细胞系中，有5种检测到MMP-13表达。这些结果表明，MMP-13特异性表达的恶性转化的鳞状上皮细胞，包括外阴SCC细胞，并出现作为其侵袭能力的标志物。
Collagenase-3 (MMP-13) is a human matrix metalloproteinase specifically expressed by invading tumor cells in squamous cell carcinomas (SCCs) of the head and neck. Here, we have further elucidated the role of MMP-13 in tumor invasion by examining its expression in invasive malignant tumors of the female genital tract. Using in situ hybridization, expression of MMP-13 mRNA was detected in 9 of 12 vulvar SCCs, primarily in tumor cells, but not in intact vulvar epithelium, in cervical SCCs (n = 12), or in endometrial (n = 11) or ovarian adenocarcinomas (n = 8). MMP-13 expression was especially abundant in vulvar carcinomas showing metastasis to lymph nodes and was associated with expression of membrane type 1 MMP by tumor cells and gelatinase-il (MMP-2) by stromal cells, as detected by immunohistochemistry. MMP-13 mRNAs were detected in 9 of 11 cell lines established from vulvar carcinomas and in 4 of 6 cell Lines from cervical carcinomas, whereas endometrial(n = 10) and ovarian (n = 9) carcinoma cell lines were negative for MMP-13 mRNA. No correlation was detected between MMP-13 expression and p53 gene mutations in vulvar SCC cell lines. However, MMP-13 expression was detected in 5 of 6 vulvar and cervical SCC cell lines harboring HPV 16 or 68 DNA. These results show that MMP-13 is specifically expressed by malignantly transformed squamous epithelial cells, including vulvar SCC cells, and appears to serve as a marker for their invasive-capacity.