Part of what makes cancer so hard to fight is the Whack-A-Mole game it can present. Even if the primary tumor is removed, the disease may have already spread, popping up again and again in different parts of the body. Now, scientists at the Scripps Research Institute have identified a protein that fuels this process of metastasis, and found that reducing the levels of that protein can help keep a tumor locked down.
Transforming growth factor beta (TGF-β) is a signaling protein that normally controls the growth of healthy cells, but cancer can break the rules thanks to a mutation that allows them to spread and evade detection by the immune system. That makes TGF-β a good potential target to help combat cancer, with scientists recently engineering new T-cells to suppress the protein and track down these cloaked cancer cells.
The problem is that TGF-β also has some positive functions in the body, so completely suppressing the protein isn't an option. Instead, the Scripps researchers focused their efforts further "upstream", on a related protein called Latent TGF-β Binding Protein 3 (LTBP3). This protein is known to regulate TGF-β, so the team experimented to see what role it might play in cancer metastasis.
The Scripps scientists used chick embryo and rodent models of cancers, creating human tumor cell lines that modeled prostate carcinoma, head and neck carcinoma and fibrosarcoma. In each of these, the researchers blocked the expression and secretion of LTBP3, and found that the primary tumors weren't able to metastasize.
"Specifically, LTBP3 appears to help tumors grow new blood vessels in a process called angiogenesis, which is critical for tumor cell intravasation," says Elena Deryugina, first author of the study. "That is when cancer cells enter into blood vessels of defined size and permeability."
The find suggests that LTBP3 helps tumors quickly grow new blood vessels and begin to metastasize at an early stage. Identifying this protein gives researchers a new target for stopping cancer from spreading very early on, improving survival rates for those with certain kinds of tumors. Blocking LTBP3 directly should also minimize the treatment's impact on the positive functions of TGF-β in the body.
In future, the team plans to further study the relationship between LTBP3 and TGF-β.
The research was published in the journal Oncogene.
Source: Scripps Research Institute
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