Boston, Mass.By studying the roles two proteins, thrombospondin-1 and prosaposin, play in discouraging cancer metastasis, a trans-Atlantic research team has identified a five-amino acid fragment of prosaposin that significantly reduces metastatic spread in mouse models of prostate, breast and lung cancer. The findings suggest that a prosaposin-based drug could potentially block metastasis in a variety of cancers.
The study team, led by Randolph Watnick, PhD, at Boston Children's Hospital, Vivek Mittal, PhD, at Weill Cornell Medical College and Lars Akslen, MD, PhD, at the University of Bergen, released their findings in the May issue of the journal Cancer Discovery.
The main cause of cancer mortality is not the primary tumor itself, but rather its spreadmetastasisto other locations in the body and subsequent organ failure. Previous studies by Watnick, a member of Boston Children's Vascular Biology Program, and others have shown that tumors capable of metastasis release proteins that help prepare new homes in distant organs for their metastatic progeny.
Watnick's lab has also previously shown that tumors that cannot metastasize release prosaposin. This protein activates expression of a second protein called thrombospondin-1, a potent anti-angiogenic factor, in tissues where metastatic tumor cells could potentially take root. Thrombospondin-1 makes these otherwise-permissive tissues resistant to metastasis.
"In the past, we've struggled to determine the source of thrombospondin-1 production," Watnick says. "We knew it was coming from the tumor microenvironment, normal cells adjacent to the sites of potential metastasis, but we could not tell if those cells were native to the microenvironment or had been recruited from the bone marrow."
Using mouse models of breast, prostate and lung cancer, Watnick and his colleagues confirmed through bone marrow transplant and gene knockout experiments that both metastatic an
|Contact: Keri Stedman|
Boston Children's Hospital