Subhamoy Dasgupta

What Drives Painful Bone Metastasis in Prostate Cancer, and Can it Be Prevented?

Roswell Park team uncovers possible strategy for blocking prostate tumor growth in bone

  • People with prostate cancer often face painful bone metastases
  • Study identifies enzyme vital to the metastatic growth of prostate cancer cells
  • Findings reveal potential strategy for treating bone-metastatic prostate cancer

BUFFALO, N.Y. — While prostate cancer originates within the prostate, metastasis, or the spread of a tumor from the site of origin to other organs, remains a leading cause of death among people with the disease. Prostate tumors can metastasize to a number of different organs, including the liver, lymph nodes and bone.

People with advanced prostate cancer often develop bone metastases — lesions of prostate cancer growing on distant bones — that are very painful and difficult to treat. Given the significant differences between the microenvironments surrounding the bone and prostate, a team from Roswell Park Comprehensive Cancer Center set out to learn more about how prostate tumors survive and grow in the bone.

Led by Subhamoy Dasgupta, PhD, Assistant Professor of Oncology in Roswell Park’s Department of Cell Stress Biology, the team determined that prostate tumors change their metabolism to produce more fats, which helps them survive within the bones. The team’s findings have been published online in Cancer Research, a journal of the American Association for Cancer Research.

Data from this study suggest that a mitochondrial enzyme called aconitase plays a key role in the development and viability of prostate cancer cells. The Roswell Park research team discovered that prostate tumors are able to alter their metabolism and produce additional fats by stimulating this enzyme. 

“There’s a fundamental gap in knowledge regarding how prostate tumor cells survive inside the bone,” explains Dr. Dasgupta, senior author of the new work. “In this study, we provide evidence that prostate tumor cells alter their mitochondrial metabolism to increase synthesis of fats, which serve as a sort of food source enabling the prostate cells to take root and survive in a new location.”

The team reports that activation of aconitase is enabled by suppressing a deacetylase enzyme named sirtuin-3, or SIRT3, resulting in increased lipid synthesis.

Previous studies have associated increased expression of another protein, SRC-2, with aggressive prostate cancer. In the current study, Dr. Dasgupta and colleagues determined that patients with high SRC-2 in their tumors simultaneously saw low expression of SIRT3, helping those aggressive tumors to spread to new sites. Through their preclinical work in the lab, the investigators showed that the loss of SRC-2 significantly reduced metastatic growth of prostate cancer cells in the bone microenvironment.

The team’s findings highlight the importance of mitochondrial metabolic adaptation in the growth of advanced bone metastatic prostate cancer, and suggest that blocking SRC-2 in order to enhance SIRT3 expression may be a viable treatment strategy.

“This is an early-stage discovery identifying potential pathways that could be targeted to block prostate tumor growth inside the bone,” notes Dr. Dasgupta. “We’ve begun additional work to investigate the clinical benefits of our research findings and identify particular drugs or new agents that could block this pathway.”

Abhisha Sawant Dessai, a predoctoral trainee, and Mayrel Palestino Dominguez, PhD, a Postdoctoral Fellow, both from Dr. Dasgupta’s lab team, are co-first authors on the paper.

This work was supported by grants from the National Cancer Institute (project numbers K22CA207578, P30CA016056 and DP2CA260421, the NIH Director’s New Innovator Award) and Department of Defense (award number W81XWH-16-1-0297, and by donations to Roswell Park.


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