Kurahara S, Shinohara M, Ikebe T, Nakamura S, Beppu M, Hiraki A, Takeuchi H, Shirasuna K
Second Department of Oral and Maxillofacial Surgery Faculty of Dentistry, Kyushu University, Fukuoka, Japan.
Head Neck. 1999 Oct;21(7):627-38. doi: 10.1002/(sici)1097-0347(199910)21:7<627::aid-hed7>3.0.co;2-2.
Matrix metalloproteinases (MMPs) that degrade the extracellular matrices (ECMs) have been thought to play an important role in both the invasion and metastasis of tumors. However, the detailed role of MMPs and TIMPs (tissue inhibitors of MMP) on the biological behavior of tumor cells has yet to be elucidated in vivo. The aim of the present study was thus to determine whether expression of MMPs on tumor cells is associated with such clinicopathological features as the invasive and metastatic potential.
This study included 96 cases of primary oral squamous cell carcinoma (OSCC), of which 38 cases showed lymph node metastases. The relationship between the expression of MMPs and the staining of ECMs, the mode of tumor invasion, nodal involvement, and expression of TIMPs was immunohistochemically examined.
First of all, a decrease in the staining of ECMs was observed in cases with an increased expression of MMP-1, -2, and -9. The association between the expression of MMPs and the loss of ECMs was thus found to be statistically significant. Secondly, in both invasive and metastatic cases, a marked expression of MMP-1, -2, -3, -9 and MT1-MMP was frequently observed. The association of the expression of MMPs both with the mode of tumor invasion and nodal involvement was thus found to be statistically significant. Thirdly, TIMP-2 was thus found not to significantly decrease in metastatic cases, while TIMP-1 expression significantly increased in metastatic cases.
These results suggest that tumor progression is dependent on the ability of tumor cells to degrade ECMs, while the metastasis of tumors is regulated by many types of MMPs, and the overproduction of MMPs therefore appears to be more important for metastasis than the production of TIMPs in vivo.
基质金属蛋白酶（MMPs）可降解细胞外基质（ECMs），被认为在肿瘤侵袭和转移中起重要作用。然而，MMPs和基质金属蛋白酶组织抑制剂（TIMPs）对肿瘤细胞生物学行为的具体作用在体内尚未阐明。因此，本研究的目的是确定肿瘤细胞上MMPs的表达是否与侵袭和转移潜能等临床病理特征相关。
本研究纳入96例原发性口腔鳞状细胞癌（OSCC），其中38例有淋巴结转移。采用免疫组织化学方法检测MMPs表达与ECMs染色、肿瘤侵袭方式、淋巴结受累情况及TIMPs表达之间的关系。
首先，在MMP-1、-2和-9表达增加的病例中观察到ECMs染色减少。因此，发现MMPs表达与ECMs缺失之间的关联具有统计学意义。其次，在侵袭性和转移性病例中，经常观察到MMP-1、-2、-3、-9和MT1-MMP的显著表达。因此，发现MMPs表达与肿瘤侵袭方式和淋巴结受累情况之间的关联具有统计学意义。第三，发现TIMP-2在转移性病例中无显著降低，而TIMP-1表达在转移性病例中显著增加。
这些结果表明，肿瘤进展取决于肿瘤细胞降解ECMs的能力，而肿瘤转移受多种MMPs调节，因此在体内MMPs的过度产生似乎比TIMPs的产生对转移更为重要。
