Promising Noninvasive Cellular Phenotype in Prostate Cancer Cells Knockdown of Matrix Metalloproteinase 9

Gupta, Aditi; Cao, Wei; Sadashivaiah, Kavitha; Chen, Wantao; Schneider, Abraham; Chellaiah, Meenakshi A.

doi:10.1155/2013/493689

Cited by 28 publications

(25 citation statements)

References 48 publications

(72 reference statements)

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“…3 a). It is possible that the antibodies have a difficult time recognizing CD44v4 and CD44v7 as an epitope, possibly due to glycosylation or some other post-translational modifications that mask antibody binding sites [ 25 , 26 ]. It is surprising that PC3-EMT elicits any CD44v6 expression since it is undetectable at the western and qPCR levels.…”

Section: Discussionmentioning

confidence: 99%

Alternative CD44 splicing identifies epithelial prostate cancer cells from the mesenchymal counterparts

et al. 2015

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An epithelial to mesenchymal transition (EMT) has been shown to be a necessary precursor to prostate cancer metastasis. Additionally, the differential expression and splicing of mRNAs has been identified as a key means to distinguish epithelial from mesenchymal cells by qPCR, western blotting and immunohistochemistry. However, few markers exist to differentiate between these cells by flow cytometry. We previously developed two cell lines, PC3-Epi (epithelial) and PC3-EMT (mesenchymal). RNAseq was used to determine the differential expression of membrane proteins on PC3-Epi/EMT. We used western blotting, qPCR and flow cytometry to validate the RNAseq results. CD44 was one of six membrane proteins found to be differentially spliced between epithelial and mesenchymal PC3 cells. Although total CD44 was positive in all PC3-Epi/EMT cells, PC3-Epi cells had a higher level of CD44v6 (CD44 variant exon 6). CD44v6 was able to differentiate epithelial from mesenchymal prostate cancer cells using either flow cytometry, western blotting or qPCR.Electronic supplementary materialThe online version of this article (doi:10.1007/s12032-015-0593-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Alternative CD44 splicing identifies epithelial prostate cancer cells from the mesenchymal counterparts

et al. 2015

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“…Cells were cultured onto cover slips in a 6-or 12-well dish for 14-16 h at 37°C. Cells were immunostained with antibodies of interest or stained for actin with rhodamine phalloidin as described previously 2,6 . Cells were scanned in a Bio-Rad 6000 (Hercules, CA) confocal microscope and images were processed by the Adobe Photoshop program (Adobe Systems, Inc., Mountain View, CA).…”

Section: Immunohistochemistry and Actin Stainingmentioning

confidence: 99%

“…Actin dynamics is a critical process that modulates cellular activity via regulation of signalling pathways through receptors and cell adhesion to the extracellular matrix (ECM). CD44 is a cell surface receptor and regulator of cell migration and tumour metastasis [1][2][3][4][5] . We have shown pre viously in prostate cancer cells (PC3) that surface expression of CD44 and formation of CD44-Matrix metalloproteinase 9 (MMP9) complex generates motility enhancing signals through the degradation of ECM proteins 6,7 .…”

Section: Introductionmentioning

confidence: 99%

CD44-Src signaling promotes invadopodia formation in prostate cancer (PC3) cells

Chellaiah¹

2013

OA Cancer

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IntroductionSrc kinase activation has been rep orted in unrelated human cancers and considered a possible target of anti-invasive therapies. Our aim here is to identify the relationship of Src kinase with CD44-signalling. Although CD44 is implicated in the invasion of cancer cells, its role in invadopodia formation needs further elucidation. Materials and MethodsTo study the role of Src, PC3 cells were transfected with Src constructs by adenoviral-mediated delivery. Gelatin degradation assay was performed to determine the invasive property of PC3 cells. Immunoblotting and immunostaining analyses were used to determine complex interaction of proteins with CD44. PC3 cells knockdown of CD44 were used to characterize the function of CD44 in invadopodia formation and invasion. ResultsIn this study, we show that expression of constitutively-active Src in prostate cancer 3 (PC3) cells significantly increased the invasiveness of PC3 cells via increasing the number of invadopodia as a result of CD44-associated complex (Src-Cortactin-Wiskott-Aldrich Syndrome Protein WASP) forma tion. The inhibition of invadopodial structures in CD44 knockdown PC3 cells resulted in reduced invasion. ConclusionBased on these results, we conclude that CD44-Src-cortactin-WASP is an invasion promoting complex. Proteins in this complex are relevant targets for intervening invadopodia formation and migration/invasion processes in prostate cancer cells.

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“…PI(3,4)P2 binds to the pleckstrin homology domains of Akt and PDK1 and recruits them to the plasma membrane, activating Akt. PI(3,4)P2 is present at low levels on the cell membrane and accumulates at the site of invadopodia [ 10 ], specialized structures formed in invasive cells [ 11 - 14 ]. The INPP4B substrate PI(4,5)P2 is the most abundant among the protein-interacting phosphoinositides in the plasma membrane [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

INPP4B suppresses prostate cancer cell invasion

et al. 2014

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BackgroundINPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer.ResultsWe demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine IL-8 and induced PAK6. These genes were regulated in a reciprocal manner following downregulation of INPP4B in the independently derived INPP4B-positive LNCaP prostate cancer cell line. Inhibition of PI3K/Akt pathway, which is highly active in both PC-3 and LNCaP cells, did not reproduce INPP4B mediated suppression of IL-8 mRNA expression in either cell type. In contrast, inhibition of PKC signaling phenocopied INPP4B-mediated inhibitory effect on IL-8 in either prostate cancer cell line. In PC-3 cells, INPP4B overexpression caused a decline in the level of metastases associated BIRC5 protein, phosphorylation of PKC, and expression of the common PKC and IL-8 downstream target, COX-2. Reciprocally, COX-2 expression was increased in LNCaP cells following depletion of endogenous INPP4B.ConclusionTaken together, we discovered that INPP4B is a novel suppressor of oncogenic PKC signaling, further emphasizing the role of INPP4B in maintaining normal physiology of the prostate epithelium and suppressing metastatic potential of prostate tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12964-014-0061-y) contains supplementary material, which is available to authorized users.

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Promising Noninvasive Cellular Phenotype in Prostate Cancer Cells Knockdown of Matrix Metalloproteinase 9

Cited by 28 publications

References 48 publications

Alternative CD44 splicing identifies epithelial prostate cancer cells from the mesenchymal counterparts

Alternative CD44 splicing identifies epithelial prostate cancer cells from the mesenchymal counterparts

CD44-Src signaling promotes invadopodia formation in prostate cancer (PC3) cells

INPP4B suppresses prostate cancer cell invasion

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