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

Background: 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. Methods: 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. Results: 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. Conclusion: 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.