CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth.
CD9P-1 expression correlates with the metastatic status of lung cancer, and a truncated form of CD9P-1, GS-168AT2, inhibits in vivo tumour growth.
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DOI：
10.1038/sj.bjc.6606033
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发表时间：
2011-02-01
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
CD 9表达的丧失与源自不同器官的肿瘤细胞的更高运动性和转移潜力相关。然而，这种损失的机制尚不清楚。我们产生了一个截短形式的合作伙伴1的CD 9（CD 9 P-1），GS-168 AT 2，并开发了一种新的单克隆抗体针对后者。我们测量了人肺肿瘤（hLT）中CD 9和CD 9 P-1的表达，并在体外和体内，在存在和不存在GS-168 AT 2的情况下，监测了NCI-H460中CD 9的水平。CD 9的缺失与CD 9 P-1的表达呈负相关，而CD 9 P-1的表达与hLT的转移状态相关（n=55）。在体外，GS-168 AT 2在NCI-H460的膜和细胞质中快速内化和降解，这与GS-168 AT 2与CD 9和CD 81的结合相关。在NCI-H460异种移植的裸鼠中腹膜内注射GS-168 AT 2导致肿瘤生长的剧烈抑制，以及肿瘤核心中CD 9的下调，但不导致CD 81的下调。这些发现首次表明，CD 9 P-1表达与hLT的转移状态正相关，并且CD 9 P-1表达的上调可能是实体瘤中CD 9丢失的机制之一。我们的研究还表明，在某些条件下，CD 9的丢失可能是肿瘤生长限制现象，而不是肿瘤生长促进现象。
Loss of CD9 expression has been correlated with a higher motility and metastatic potential of tumour cells originating from different organs. However, the mechanism underlying this loss is not yet understood. We produced a truncated form of partner 1 of CD9 (CD9P-1), GS-168AT2, and developed a new monoclonal antibody directed towards the latter. We measured the expression of CD9 and CD9P-1 in human lung tumours (hLTs), and monitored the level of CD9 in NCI-H460, in vitro and in vivo, in the presence and absence of GS-168AT2. Loss of CD9 is inversely related to the expression of CD9P-1, which correlates with the metastatic status of hLT (n=55). In vitro, GS-168AT2 is rapidly internalised and degraded at both the membrane and cytoplasm of NCI-H460, and this correlates with the association of GS-168AT2 with both CD9 and CD81. Intraperitoneal injections of GS-168AT2 in NCI-H460-xenografted Nude mice led to drastic inhibition of tumour growth, as well as to the downregulation of CD9, but not of CD81, in the tumour core. These findings show for the first time that CD9P-1 expression positively correlates with the metastatic status of hLT, and that the upregulation of CD9P-1 expression could be one of the mechanisms underlying the loss of CD9 in solid tumours. Our study also reveals that, under certain conditions, loss of CD9 could be a tumour growth-limiting phenomenon rather than a tumour growth-promoting one.
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影响因子：
8.7
作者：
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影响因子：
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DOI：
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发表时间：
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影响因子：
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