Loss of SPARCL1 Gene Activity Boosts Development of Aggressive Prostate Cancer

Aggressive and metastatic prostate tumors have been found to be characterized by severely reduced activity of the SPARCL1 (acidic and rich in cysteine-like 1) gene.

Investigators at Johns Hopkins University (Baltimore, MD, USA) have been trying to understand why certain types of prostate cancer patients relapse after having been "cured" by surgery. To this end, they focused the current study on the SPARCL1 gene, which had been shown to be critically important for cell migration during prostate development in the embryo and apparently becomes active again during cancer progression.

Initially, both benign and malignant prostate cancer cells express high levels of SPARCL1. However, results published in the August 27, 2012, online edition of the journal Proceedings of the National Academy of Sciences of the USA (PNAS) revealed that reduction in levels of SPARCL1 activity correlated with increased tumor aggressiveness and tendency to metastasize.

Sparcl1, a secreted protein from the acidic and rich in cysteine (SPARC) family of matricellular proteins, is present during the invasive phases of prostate development and regeneration. However, the current study demonstrated a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, SPARCL1 loss increased the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression.

“While many of our patients are initially cured with surgery, some inexplicably have their cancers return,” said senior author Dr. Edward Schaeffer, associate professor of urology, oncology, and pathology at Johns Hopkins University. “We are working to identify patients at higher risk of recurrence and our ultimate goal is to develop new treatments that would prevent the return of the cancer. Our findings should allow physicians to not only pinpoint those patients whose cancers are destined to return after surgery, but could also reveal a potential new option for treatment.”

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