Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: not an invariant correlation with metastasis.
Secretion of gelatinases and tissue inhibitors of metalloproteinases by human lung cancer cell lines and revertant cell lines: not an invariant correlation with metastasis.
复制标题
人肺癌细胞系和回复细胞系分泌明胶酶和金属蛋白酶组织抑制剂：与转移不是恒定的相关性。
DOI：
10.1002/ijc.2910520307
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发表时间：
1992
影响因子：
6.4
通讯作者：
Klein-Szanto,AJ
中科院分区：
文献类型：
--
作者：
Zucker,S;Lysik,RM;Malik,M;Bauer,BA;Caamano,J;Klein-Szanto,AJ
许多研究报告了72-kDa（MMP-2）和92-kDa（MMP-9）IV型胶原酶/明胶酶的产生与癌细胞转移潜力之间的相关性。还注意到金属蛋白酶组织抑制剂（TIMP-1和TIMP-2）对转移的消除作用。在本报告中，我们使用灵敏的酶联免疫分析法测定了8种人肺癌细胞系中MMP-2、MMP-9、TIMP-1和TIMP-2的水平，这些细胞系在裸鼠中进行了生物学行为表征。我们证明了具有最高转移、侵袭和致瘤潜力的Calu-6和A549细胞系分泌最高水平的MMP-2。MMP-9和TIMP-1分泌在所有细胞系中相对较低。TIMP-2分泌超过所有细胞系的MMP-2分泌，与转移潜能无关。为了进一步探索这些相关性，用aK‐rev‐IcDNA表达构建体转染转移性Calu‐6细胞系。K-rev回复突变体细胞系表现出分化程度更高的表型，并且在裸鼠中的致瘤性、侵袭性和转移性更低。尽管如此，Calu-6回复突变体细胞系分泌的MMP-2水平高于亲本细胞系。总之，肺癌细胞的侵袭和转移不仅需要增强MMP的产生，还需要其他不太清楚的致瘤特征。癌细胞扩散所需的多种因素有助于解释原发性肿瘤中微小部分的癌细胞发展为转移。© 1992 Wiley利斯公司
Numerous studies have reported a correlation between production of 72‐kDa (MMP‐2) and 92‐kDa (MMP‐9) type‐IV collagenases/gelatinases and the metastatic potential of cancer cells. An abrogating effect of tissue inhibitors of metalloproteinases (TIMP‐1 and TIMP‐2) on metastases has also been noted. In this report we have used sensitive enzyme‐linked immunoas‐says to measure MMP‐2, MMP‐9, TIMP‐1 and TIMP‐2 levels in eight human lung‐cancer cell lines which were characterized for biological behavior in nude mice. We demonstrated that the Calu‐6 and A549 cell lines with the highest metastatic, invasive and tumorigenic potential secreted the highest levels of MMP‐2. MMP‐9 and TIMP‐1 secretions were comparatively low in all cell lines. TIMP‐2 secretion, which exceeded MMP‐2 secretion for all cell lines, did not correlate with metastatic potential. To further explore these correlations, the metastatic Calu‐6 cell line was transfected with aK‐rev‐IcDNA expression construct. The K‐rev revertant cell lines demonstrated a more differentiated phenotype and were less tumorigenic, invasive and metastatic in nude mice. Nonetheless, the Calu‐6 revertant cell lines secreted higher levels of MMP‐2 than the parent cell line. In conclusion, invasion and metastasis by lung‐cancer cells requires not only enhanced MMP production, but also other less well‐understood tumorigenic characteristics. The multiplicity of factors required by cancer cells for dissemination helps to explain the minute fraction of cancer cells from a primary tumor that ever develop into a metastasis. © 1992 Wiley‐Liss, Inc.