Randolph Watnick of Boston Children's Hospital, Vivek Mittal at Weill Cornell Medical College in New York and Dr. Lars Akslen at the University of Bergen in Norway said the findings suggest an amino acid-based -- prosaposin -- drug could potentially block metastasis in a variety of cancers.
The main cause of cancer mortality is not the primary tumor itself, but rather its spread, or metastasis, to other locations in the body and subsequent organ failure, Watnick said.
Previous studies by Watnick and others showed tumors capable of metastasis release proteins that help prepare new homes in distant organs for their metastatic progeny.
Watnick's lab also showed tumors that cannot metastasize release prosaposin and this protein activates expression of a second protein -- thrombospondin-1 -- in tissues where metastatic tumor cells could potentially take root. Thrombospondin-1 makes these otherwise-permissive tissues resistant to metastasis, the study said.
Using mouse models of breast, prostate and lung cancer, Watnick and colleagues confirmed via bone marrow transplant and gene knockout experiments both metastatic and non-metastatic tumors induce cells from the bone marrow -- specifically, monocytes expressing the Gr1 surface marker -- to migrate to the lungs.
However, non-metastatic tumors then trigger these monocytes to produce thrombospondin-1 by releasing prosaposin.
"Others have shown that tumors recruit monocytes to future metastatic sites, which help to set up a permissive environment for tumor cells to metastasize," Watnick said.
"Our results suggest that non-metastatic tumors do the same thing, but instead of creating a permissive environment, the monocytes create a refractory environment by producing thrombospondin-1."
The findings were published in the journal Cancer Discovery.
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