Prostate Cancer Stem Cells Regulated by Specific MicroRNA

A class of microRNA (miRNA) has been found that specifically interacts with a prostate cancer cell-surface protein and interferes with tumor growth and metastasis.

Investigators at the University of Texas MD Anderson Cancer Center (Houston, USA) studied prostate cancer stem cells (CSCs) under a variety of in vivo and in vitro conditions. In particular, they were interested in the role of the miRNA known as miR-34a in the progression of the disease.

CSCs in many tumors have been identified using the cell surface adhesion molecule CD44. Prostate CSCs with enhanced tumor-initiating and metastatic capacities are enriched with CD44, but whether miRNAs regulate CD44+ prostate cancer cells and prostate cancer metastasis has been unclear. This point has now been clarified in a report published in the January 16, 2011, online edition of the journal Nature Medicine.

The investigators used expression analysis to show that miR-34a was underexpressed in CD44+ prostate cancer cells purified from human xenograft tumors growing in mice and in primary tumors in patients. Enforced expression of miR-34a in cultures of CD44+ prostate cancer cells inhibited clonogenic expansion, tumor regeneration, and metastasis. In contrast, suppression of miR-34a in CD44+ prostate cancer cells promoted tumor development and metastasis. Systemically delivered miR-34a inhibited prostate cancer metastasis and extended survival of tumor-bearing mice.

"CD44 has long been linked to promotion of tumor development and, especially, to cancer metastasis Many cancer stem cells overexpress this surface adhesion molecule,” said senior author Dr. Dean Tang, professor of molecular carcinogenesis at the University of Texas MD Anderson Cancer Center. "Another significant finding from our study is identifying CD44 itself as a direct and functional target of miR-34a. Our findings are the first to profile a microRNA expression pattern in prostate cancer stem cells and also establish a strong rationale for developing the microRNA miR-34a as a new treatment option for prostate cancer."

"There are many companies developing microRNA-based drugs," said Dr.Tang. "Delivery of miRNAs is a challenge, but the field is moving fast through the preclinical stage.”

Related Links:
University of Texas MD Anderson Cancer Center