Expression of collagenases-1 and -3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas.
Expression of collagenases-1 and -3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas.
复制标题
胶原酶-1和-3及其抑制剂TIMP -1和-3的表达与恶性黑色素瘤的浸润水平相关。
DOI：
10.1038/sj.bjc.6690417
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发表时间：
1999-05
影响因子：
8.8
通讯作者：
Saarialho-Kere, UK
中科院分区：
文献类型：
--
作者：
Airola, K;Karonen, T;Vaalamo, M;Lehti, K;Lohi, J;Kariniemi, AL;Keski-Oja, J;Saarialho-Kere, UK
由于皮肤黑色素瘤的局部侵袭生长和早期转移形成需要真皮胶原基质和基底膜的蛋白分解，我们用原位杂交和Northern分析方法分析了某些金属蛋白酶在黑色素瘤和培养的黑色素瘤细胞中的活性和表达水平。除了胶原酶-1和-3与多种恶性肿瘤的侵袭性生长行为有关外，我们还分析了培养的黑色素瘤细胞中72-kDa明胶酶及其激活物MT1-MMP和TIMP-2的水平。其中恶性雀斑3例，Clark I-V级黑色素瘤28例。癌前肿瘤和I级肿瘤的胶原酶-1和-3和TIMP-1和-3始终为阴性。胶原酶主要在Clark III和IV级肿瘤的癌细胞中表达。TIMP-1和TIMP-3在III级和IV级黑色素瘤的癌细胞和(或)间质细胞中大量表达，而TIMP-2蛋白也在黑色素瘤中表达，具有较低的侵袭性。对7个黑色素瘤细胞株的Northern分析表明，胶原酶-1、TIMPS-1和-3的表达与72 kDa明胶酶阳性有关。所有黑色素瘤细胞系均表达MTI-MMPs和TIMP-2mRNAs。我们的结果表明，胶原酶-1和-3以及TIMPS-1和-3的过度表达在黑色素瘤的进展过程中被诱导。TIMPs的表达可能反映了宿主对肿瘤侵袭的反应，从而努力控制基质金属蛋白酶的活性，保护细胞外基质的完整性。©1999癌症研究活动
Since proteolysis of the dermal collagenous matrix and basement membranes is required for local invasive growth and early metastasis formation of cutaneous melanomas, we have analysed the activities/expression levels of certain metalloproteinases in melanomas and cultured melanoma cells by in situ hybridization and Northern analysis. In addition to collagenases-1 and -3 that have been implicated in invasive growth behaviour of various malignant tumours, we analysed the levels of 72-kDa gelatinase and its activators MT1-MMP and TIMP-2 in cultured melanoma cells. The lesions examined included three cases of lentigo maligna and 28 cases of Clark grade I–V melanomas. The premalignant as well as the grade I tumours were consistently negative for collagenase-1 and -3 and TIMP-1 and -3. The collagenases were predominantly expressed in the cancer cells of Clark grade III and IV tumours. TIMP-1 and -3 were abundantly expressed in the cancer and/or stromal cells of grade III and IV melanomas, while TIMP-2 protein was detected also in melanomas representing lower invasive potential. Northern analysis of seven melanoma cell lines showed that the expression of collagenase-1 and TIMPs-1 and -3 was associated with 72-kDa gelatinase positivity. All melanoma cell lines were positive for MTI-MMP and TIMP-2 mRNAs. Our results suggest that overexpression of collagenases-1 and -3 and TIMPs -1 and -3 is induced during melanoma progression. Expression of TIMPs may reflect host response to tumour invasion in an effort to control MMP activity and preserve extracellular matrix integrity. © 1999 Cancer Research Campaign
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影响因子：
5.6
作者：
JOHNSON, MD;KIM, HRC;POLVERINI, PJ
通讯作者：
POLVERINI, PJ
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
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SACCHI, N
影响因子：
6.4
作者：
HOYHTYA, M;HUJANEN, E;TRYGGVASON, K
通讯作者：
TRYGGVASON, K
影响因子：
9
作者：
BRESLOW, A
通讯作者：
BRESLOW, A