October 18, 2018

Interaction in prostate cancer may explain disease growth once cells reach bone in patients

Sreenivasa Chinni, Ph.D.

Cancer researchers at the Wayne State University School of Medicine have found a novel interaction between a receptor and a lipid in prostate cancer cells that may explain why the disease grows once it spreads to bone.

"Our study indicates that when prostate cancer cells arrive in the bone, the activation of lipid kinase may participate in the growth of the cancer cells in bone," said lead investigator Sreenivasa Chinni, Ph.D., an associate professor of Urology, of Pathology and of Oncology.

The prostate cancer patient responds to primary therapies when cancer remains localized in the prostate tissues, but patients develop advanced disease when cancer spreads to bone. Patients with bone metastasis die due to complications, despite available therapies that extend life.

"The current therapies are not curative. Identifying novel therapies to target bone tumor growth may aid the patient in living longer with bone metastasis. In other words, (we hope to) keep these bone tumors dormant with novel therapies in these patients," Dr. Chinni said.

The normal function of lipid kinase, or PI4KIIIa, is to maintain the integrity of plasma membrane in cells. "A novel cross-talk between CXCR4 and KI4KIIIa in prostate cancer cells," published in the August issue of Oncogene, a Nature Publishing Group journal, marks the first time the lipid's potential role in cell invasion and prostate cancer metastasis was revealed.

"We have previously shown that chemokines, which are small peptides expressed in bone tissue, recruit prostate cancer cells by binding and activating through their receptor CXCR4," Dr. Chinni said. "To further gain novel insights on how chemokine causes the prostate cancer to spread, we performed a proteomics analysis on cancer cells and found that the receptors on cancer cells activate a novel lipid kinase. We have shown in the manuscript that chemokines receptors activate these lipid kinases, and this activity signals the prostate cancer cells to exit from the primary site to bone to develop metastasis. Interestingly, analysis of this lipid kinase with tumor tissue expressed genes showed that lipid kinase expressed at very high levels in prostate cancers are spread to distant organs in patients."

Further experiments are in progress to evaluate whether this lipid kinase is a suitable target for growth metastasis tissues. They want to determine the biological significance of lipid kinase activation on bone tumor growth using a mouse model.

Dr. Chinni's research team on the project included Diego Sbrissa, a post-doctoral fellow who heavily contributed to the project; technician Louie Semaan; and Barani Govindarajan, a third-year graduate student in the Department of Pathology, as well as faculty members from the departments of Pathology, Oncology and Physiology.