July 13, 2024

Identified: The Key Gene Responsible for Metastasis in Prostate Cancer

Researchers from the Virginia Commonwealth University have made a groundbreaking discovery, identifying the gene that triggers a chain reaction leading to the metastasis of prostate cancer to the bone. Metastasis refers to the spread of cancer cells from the primary tumor to distant sites in the body, making the disease much harder to treat. This discovery could have significant implications for the treatment of prostate cancer and other solid tumor types where this gene is present.

Bone metastases are particularly common in advanced prostate and breast cancers and are often associated with poor prognosis. When prostate cancer spreads to the bone, it typically becomes a death sentence due to the lack of effective therapies. The growth and spread of prostate cancer involve complex interactions between tumor cells and the surrounding microenvironment. Researchers have long known that a specific gene called melanoma differentiation-associated gene-9 (MDA-9) plays a major role in cancer spread, but the exact mechanism was not fully understood.

In a recent study, researchers at the Virginia Commonwealth University Massey Comprehensive Cancer Center and the VCU Institute of Molecular Medicine examined the role of MDA-9 in the metastasis of prostate cancer. They discovered, for the first time, how this gene triggers a chain reaction leading to metastasis and allows tumor cells to take control within the bone.

MDA-9 essentially facilitates tumor progression and metastasis, making it a key player in the spread of the cancer, according to Swadesh Das, a co-corresponding author of the study.

The researchers identified a multi-step pathway involving MDA-9. The gene activates platelet-derived growth factor AA (PDGF-AA) in tumor cells, which is a protein that regulates cell growth and division. PDGF-AA is then released into the bone environment, where it binds with receptors on bone marrow-mesenchymal stromal cells (BM-MSCs). These cells are important for making and repairing skeletal tissues. The interaction between MDA-9 and the stromal cells activates the Hippo signaling pathway, which is responsible for cell regeneration. This activation leads to the release of a smaller migration-stimulating protein called chemokine CXCL5. CXCL5 attracts cancer cells into the bone tissue, and this cycle continues, with more CXCL5 being produced and more cancer cells being lured into the bone. Additionally, CXCL5 enhances the reproduction of osteoclasts, a subset of bone cells that destroy bone.

This study provides clear evidence of communication between prostate cancer cells and normal BM-MSCs within the tumor microenvironment, and how this communication allows metastatic cells to spread and proliferate in bone, according to Das.

The researchers found that by inhibiting MDA-9 in prostate cancer cells, they were able to interrupt this chain reaction, preventing the spread of the disease. It was also observed that removing MDA-9 from bone cells did not have any negative effects on bone tissue health.

While the study focused on prostate cancer, the researchers believe that their findings could have implications for other solid tumor types where MDA-9 is present, including brain, breast, melanoma, lung, and pancreatic cancers.

The researchers have also developed a novel inhibitor drug in collaboration with InVaMet Therapeutics, which shows promise in targeting MDA-9 in cancer. They are hopeful that this drug could eventually be used in clinical settings and benefit patients.

“We’re close to something that may go into the clinic,” said Paul Fisher, another corresponding author. Future studies will investigate the use of MDA-9 inhibitors in clinical tumor samples and, ultimately, in patients.

*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it