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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.

ABSTRACT: 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.

SUBMITTER: Guilmain W

PROVIDER: S-EPMC3049554 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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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.

Guilmain W W Colin S S Legrand E E Vannier J P JP Steverlynck C C Bongaerts M M Vasse M M Al-Mahmood S S

British journal of cancer 20110104 3

<h4>Background</h4>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.<h4>Methods</h4>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, ...[more]

PMID: 21206492

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Project description:BACKGROUND:The prognostic relevance of circulating tumour cells (CTCs) in metastatic breast cancer (MBC) patients has been confirmed by several clinical trials. However, predictive blood-based biomarkers for stratification of patients for targeted therapy are still lacking. The DETECT studies explore the utility of CTC phenotype for treatment decisions in patients with HER2 negative MBC. Associated with this concept is a plethora of translational projects aiming to identify potential predictive biomarkers. The androgen receptor (AR) is expressed in over 70% of hormone receptor-positive and up-to 45% of triple-negative tumours. Studies has indicated the promising nature of AR as a new therapy target with a clinical benefit rate for anti-AR treatment in MBC patients up to 25% The aim of this analysis was the characterization of CTCs regarding the expression of the AR using immunofluorescence. METHODS:MBC patients were screened for the HER2-status of CTCs in the DETECT studies. In a subset of CTC-positive patients (n =?67) an additional blood sample was used for immunomagnetic enrichment of CTCs using the CellSearch® Profile Kit prior to transfer of the cells onto cytospin slides. Establishment of immunofluorescence staining for the AR was performed using prostate cancer cell lines LNCaP and DU145 as positive and negative control, respectively. Staining of DAPI, pan-cytokeratin (CK) and CD45 was applied to identify nucleated epithelial cells as CTCs and to exclude leucocytes. RESULTS:Co-staining of the AR, CK and CD45 according to the above mentioned workflow has been successfully established using cell lines with known AR expression spiked into the blood samples from healthy donors. For this translational project, samples were analysed from 67 patients participating in the DETECT studies. At least one CTC was detected in 37 out of 67 patients (56%). In 16 of these 37 patients (43%) AR-positive CTCs were detected. In eight out of 25 patients (32%) with more than one CTC, AR-positive and AR-negative CTCs were observed. CONCLUSION:In 43% of the analysed CTC samples from patients with MBC the AR expression has been detected. The predictive value of AR expression in CTCs remains to be evaluated in further trials.

Dataset Information

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.

Publications

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.

Similar Datasets

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