Carcinoma-Associated Fibroblasts from African American Prostate Cancer Promote Aggressive Tumors: Implications for Developing Novel Therapy
Abstract
Metabolic reprogramming is one of the key characteristics of cancer and tumor microenvironment for fueling the rapid and self-sufficient growth of cancer cells. L-3-phosphoserine phosphatase (PSPH) is one of the five rate-limiting enzymes in the biosynthesis of serine from glucose. We are the first to show that PSPH is overexpressed in carcinoma associated fibroblasts (CAFs) and cancer tissues of African American (AA) prostate cancer (PCa) compared to those of European American (EA) PCa and distant carcinoma associated fibroblasts (dCAFs). High PSPH mRNA levels predict poor survival of prostate cancer. Knocking down the expression of PSPH in PCa DU145 cell line exhibits slow growth and overexpression of PSPH in benign associated prostate fibroblasts promote cell growth. In addition, we have developed primary cultures of 119 EA CAFs and matched BAFs and 39 AA CAFs and matched BAFs. Preliminary studies show that AA CAFs can transform tumorigenic growth and promote metastasis of benign prostate epithelial cells BPH-1 by co-inoculation in sub-Renal capsule xenograft experiment. The results suggest that PSPH may be a new target for treatment of PCa and AACAFs may promote the aggressiveness of PCa.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1125495
Entities
People
- Michael Lilly
- Xiaolin Zi
Organizations
- University of California, Irvine