Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer

Tetraspanin transmembrane proteins have a metastasis suppressor effect by acting as cell motility brakes in tumor cells. CD53 is a panleukocyte antigen that belongs to the tetra-span superfamily. Human neutrophils express high levels of CD53. We tested the hypothesis that this antigen level changes when cells are activated. Treatment of human neutrophils with their physiological activators, tumor necrosis factor ␣ or platelet-activating factor, resulted in down-regulation of this antigen from the cell surface, as assessed by immunofluorescence flow cytometry. Similar responses were observed when neutrophils were stimulated with chemotactic N-formyl-methionyl-leucyl-phenylalanine, phorbol ester, or the calcium ionophore ionomycin. The CD53 antigen down-regulation upon neutrophil stimulation was further confirmed by immunoblotting analysis and was not correlated with a change in the level of CD53 transcripts. This CD53 antigen down-regulation paralleled that of CD43 and CD44 antigens in these cells, despite their different protein structure. The down-regulation of the three antigens CD53, CD43, and CD44 could be inhibited by phenylmethylsulfonyl fluoride, suggesting that CD53 antigen down-regulation is the result of the activation of a proteolytic mechanism. Down-regulation of CD53 antigen level, as a result of cellular stimulation, might play a role in the different aspects of neutrophil biology, by modulating its interactions on the cell surface.

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Physiological activation of human neutrophils down-regulates CD53 cell surface antigen

Mollinedo

Martı́n-Martı́n

Gajate

et al. 1998

Journal of Leukocyte Biology

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Neutral endopeptidase/CD10 andAminopeptidase N/CD13 gene expression as a prognostic factor in non-small cell lung cancer

Tokuhara

Adachi

Hashida

et al. 2001

Jpn J Thorac Caridovasc Surg

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Role of CD9 in proliferation and proangiogenic action of human adipose-derived mesenchymal stem cells

Kim

Joo

et al. 2007

Pflugers Arch - Eur J Physiol

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CD9 belongs to the tetraspanin family and is involved in cell motility, osteoclastogenesis, metastasis, neurite outgrowth, myotube formation, and sperm-egg fusion. CD9 also promotes juxtacrine signaling involved in proliferation and attachment. Varying degrees of CD9 expression have been found in human mesenchymal stem cells. In this study, we determined the functional roles of CD9 in human adipose-derived mesenchymal stem cells (hASCs). The CD9 expression in hASCs was down-regulated during culture expansion. A colony-forming unit assay revealed that the clonal expandability of hASCs was directly correlated with the CD9 expression level of the colony. The CD9(high) cells exhibited an increased ability to proliferate, increased cell adhesiveness, and better in vitro tube formation than the CD9(low) cells. The cellular proliferation and attachment of the CD9(high) cells were inhibited upon treatment with a blocking antibody against CD9 and the transduction of a CD9 miRNA lentivirus. The CD9(high) cells showed higher NF-kappaB promoter activity and higher levels of intercellular adhesion molecule 1 than the CD9(low) cells. Reverse transcription-polymerase chain reaction analysis revealed higher endothelial nitric oxide synthase expression in the CD9(high) cells than in the CD9(low) cells. The engraftment and the proangiogenic action of hASCs in a murine model of hindlimb ischemia were significantly higher in the CD9(high) cells than in the CD9(low) cells. This study indicates that CD9 plays roles in cell proliferation and attachment in vitro as well as in in vivo engraftment and that it can be considered as a useful marker to predict the in vivo efficacy of hASCs.

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Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer

Cited by 26 publications

References 26 publications

Physiological activation of human neutrophils down-regulates CD53 cell surface antigen

Physiological activation of human neutrophils down-regulates CD53 cell surface antigen

Neutral endopeptidase/CD10 andAminopeptidase N/CD13 gene expression as a prognostic factor in non-small cell lung cancer

Role of CD9 in proliferation and proangiogenic action of human adipose-derived mesenchymal stem cells

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