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Prostate Cancer Cell-derived Exosomes Enable Androgen Production By Patients Derived Stem Cells: Exploring Racial Disparity And Targeting Residual Androgen Through Stem Cell-based Selective Delivery Of 3α-hsd

Prostate cancer is the most common cancer occurring in the men in USA and Europe. According to CDC, incidence of Prostate cancer in African American men in the year 2008 was 234.6 cases per 100,000 compared to 150 cases per 100,000 in Caucasian men, reasons for this disparity remain unclear. Castration resistant prostate cancer is an advanced form of prostate cancer with poor survival rates. 10-20% of prostate cancer patients develop metastatic castration resistant prostate cancer (CRPC) within approximately 5 years of follow-up. Androgen deprivation therapy which is at the center of metastatic prostate cancer is often impeded by development of CRPC. Previous studies have demonstrated that prostatic androgen concentration ranging between 10-25 percent in the treated patients versus the untreated could still continue AR signaling. Previous in vitro studies have demonstrated higher tumor homing potential in normal adipose derived mesenchymal stem cells (ADMSC) from African American patient compared to ADMSC derived from a Caucasian patient when grown in prostate cancer cell condition media. This study attempts to exploit this tumortropicity of ADMSC for selective delivery of alpha keto reductases in the metastasized prostate cancer cells to hydrolyse DHT and other androgens into weaker androgens. Enriched ADMSC were plated in a 6 well plate and were co-transfected with transfected with AKRC14 and GFP. Gene expression was confirmed by PCR and WB. ADMSCs are capable of expressing AKR1C14 on transfection with plasmid. Stem cells expressing AKR1C4 open the avenues for furthering therapeutic strategies in metastatic CRPC by hydrolyzing the androgens. / 1 / Manish Ranjan

  1. tulane:45964
  2. local: td005624
Identiferoai:union.ndltd.org:TULANE/oai:http://digitallibrary.tulane.edu/:tulane_45964
Date January 2015
ContributorsRanjan, Manish (author), Abdel Mageed, Asim (Thesis advisor), School of Medicine Biomedical Sciences Graduate Program (Degree granting institution)
Source SetsTulane University
LanguageEnglish
Detected LanguageEnglish
TypeText
Formatelectronic
RightsNo embargo

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