Retraction Note to: Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

e23135 Background: Prostate Cancer (PCa) is the most common cancer in males and the second leading cause of death from cancer in men. Understanding the factors that regulate homing and survival of metastatic cancer cells in the bone is important for the identification of new therapeutic targets. High MCAM expression has been detected in the stroma of lytic and blastic lesions in preclinical models of PCa bone metastasis. The objective of this study is to characterize the role of MCAM in the maintenance of the aggressive phenotype in human PCa. Methods: We knocked and down MCAM in the lytic PC-3M-Pro4Luc2_dTomato and in the blastic C4-2B_dTomato PCa cell lines. Validation was done at both protein and RNA level. We performed functional assays such as migration and proliferation. RT-qPCR was used to test MCAM knockdown on EMT markers. The effect of the knockdown on the maintenance of cancer stem/progenitor-like cells was measured by ALDEFLUOR. Results: MCAM knockdown reduced proliferation in PC-3M-Pro4Luc2_dTomato PCa cells and resulted in increased E-Cadherin expression. Metastatic human PCa cells target the hematopoietic stem cell (HSC) niche in the bone marrow at the level of an “endosteal/osteoblast” niche and a “vascular/perivascular” niche. We set-up an in vitro model of “osteoblast niche” to study the prostate cancer cells upon co-culture with osteoblasts and to determine the effects on cancer stem/progenitor-like markers. We found that MCAM is required for the osteoblast-mediated induction of ALDH activity on PCa cells and MCAM knockdown prevented the increase in the size of the ALDHhigh subpopulation in PC-3M-Pro4Luc2_dTomato, mediated by human osteoblasts. Additionally, MCAM knockdown in PCa cells co-culture with osteoblast, prevented the induction of MCAM expression by osteoblasts. Finally, MCAM is significantly increased in the ALDHhigh cells and identifies a new subset of ALDHhigh / MCAMhigh cells which could be depleted upon MCAM knockdown. Conclusions: We detected a new subset of ALDHhigh/MCAMhigh cells and demonstrated the MCAM influences the maintenance of an aggressive-mesenchymal phenotype in human PCa. Therefore, MCAM represent an interesting target molecule to modulate the behavior of aggressive PCa cells.

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PRKC- Expression Promotes the Aggressive Phenotype of Human Prostate Cancer Cells and Is a Novel Target for Therapeutic Intervention

Genes & Cancer ◽

10.1177/1947601910376079 ◽

2010 ◽

Vol 1 (5) ◽

pp. 444-464 ◽

Cited By ~ 34

Author(s):

S. Yao ◽

A. Bee ◽

D. Brewer ◽

A. Dodson ◽

C. Beesley ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Therapeutic Intervention ◽

Human Prostate ◽

Human Prostate Cancer ◽

Prostate Cancer Cells ◽

Aggressive Phenotype ◽

Novel Target

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Intraductal carcinoma of the prostate: Precursor or aggressive phenotype of prostate cancer?

The Prostate ◽

10.1002/pros.22579 ◽

2012 ◽

Vol 73 (4) ◽

pp. 442-448 ◽

Cited By ~ 25

Author(s):

Helmut Bonkhoff ◽

Thomas M. Wheeler ◽

Theodorus H. van der Kwast ◽

Cristina Magi-Galluzzi ◽

Rodolfo Montironi ◽

...

Keyword(s):

Prostate Cancer ◽

Intraductal Carcinoma ◽

Aggressive Phenotype ◽

Carcinoma Of The Prostate

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Proteomic Profiling of Du145 Cell Line Exosomes Identifies Icam1 as Aputative molecular Mechanism by Which Relb Promotes The proliferation, Migration, and Invasion of Prostate cancer Cells

10.21203/rs.3.rs-37094/v1 ◽

2020 ◽

Author(s):

Wenjing Li ◽

Jingjing Xu ◽

Li Cheng ◽

Lianjun Zhang ◽

Qiang Shao ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Adhesion ◽

Molecular Mechanism ◽

Intercellular Adhesion Molecule ◽

Migration And Invasion ◽

Label Free ◽

Proteomic Profiling ◽

Intercellular Adhesion Molecule 1 ◽

Aggressive Phenotype ◽

Du145 Cells

Abstract Background: Prostate cancer (PC) is a serious health issue in men. Exosome plays essential roles in modulating the oncogenesis and progression of PC. RelB is highly expressed in PC and plays oncogenic parts in DU145 cells. We aim to uncover the protein panel of exosomes derived from RelB-knockdown DU145 cells (siRelB) as compared to control cells (sictrl) and explore a potential mechanism that RelB conferring the more aggressive phenotype to DU145 cells.Methods: Exosomes derived from sictrl and siRelB were subjected to Liquid Chromatography-Mass Spectrometry for proteomics profiling. Label-free quantification strategy iBAQ (intensity-based absolute quantification) was used to quantify and Fold Change (FC) was calculated to identify the differentially expressed proteins (DEPs). The characterization of proteins was conducted by bioinformatics analysis. ICAM1 over-expressing DU145 cells (hICAM1) and control cells (hctrl) were established by transfection using Lipofectamine 2000. The cell growth, migration, and invasion capabilities were measured by the xCelligence real-time monitoring system. Annexin V/PI-staining was adopted to assess apoptosis. CCK-8 assay was applied for proliferation evaluation. Integrin β-1, MMP9, and uPA were detected by Western blot.Results: 1259 exosomal proteins were identified, with 160 and 105 proteins unique to the siRelB and sictrl, respectively, while 994 proteins were present in both. We identified 137 upregulated and 55 downregulated proteins in siRelB. Gene Ontology (GO) analysis revealed that some DEPs had the cell adhesion molecular activity and participated in the cell adhesion process. Kyoto Encyclopedia of Genes and Genomes (KEGG) enriched that intercellular adhesion molecule-1 (ICAM1) was downregulated targeted by the NF-κB signaling. The FC of exosomal ICAM1 was 2.136. The expression of ICAM1 was positively related to RelB in PC by UALCAN. ICAM1 was shown to be co-expressed with RelB by GeneMANIA. The protein abundance of exosomal ICAM1 was lower in siRelB. hICAM1 had enhanced abilities of proliferation, migration, and invasion, with higher expression of Integrin β-1 when compared to hctrl.Conclusions: Our study identified 192 exosomal DEPs downstream of RelB in the DU145 cells. Exosomal ICAM1, conferring a more aggressive phenotype to DU145 cells, is a potential molecular mechanism modulating the tumorigenesis and progression of PC cells.

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