the growth of healthy tissues in the body depends on the development of new blood vessels, a process called angiogenesis, that enable proper blood flow, meaning nutrients and oxygen are delivered while toxic metabolic products are removed. But solid tumors grow faster than healthy tissues, resulting in deficiencies in oxygen and blood flow, which leads to accelerated formation of dysfunctional blood vessels. Malignant cells rapidly grow while antitumor immune cells quickly lose their viability and function.

These events, cell biologist Serge Fuchs of the School of Veterinary Medicine says, promote generation of the immunosuppressive tumor microenvironment, which stimulates the spread and growth of tumors and confers resistance to antitumor therapies.

Past research has shown how native C-type natriuretic peptide (CNP), a 22-amino acid peptide produced by endothelial cells and fibroblasts, stimulates growth of normal blood vessels and restores proper blood flow and oxygenation within tissues of rodent limbs that weren’t getting enough blood flow. Given the importance of CNP in angiogenesis, researchers reasoned that CNP would also play a critical role in regulating tumor vasculature. But therapeutic potential of CNP is severely hampered by its short half-life of less than three minutes, says Zhen Lu, a former senior research investigator in Fuchs’ lab.

Fuchs and Lu are part of an interdisciplinary, collaborative team which found that modifying CNP stimulated the formation of blood vessels, increased blood flow through tissue, reinvigorated antitumor immune responses, and slowed growth of tumors in an animal model. The results published in the journal Science Translational Medicine suggest that the treatment could alleviate hypoxia, or insufficient oxygen levels, in tumors. The team includes researchers from Kyushu University, the Higashiosaka City Medical Center, the Case Western Reserve University School of Medicine, and PharmaIN Corp.

“It is a successful approach to target the immunosuppressive tumor microenvironment, which should lead to a breakthrough in treatment of a large variety of solid tumors,” says Fuchs, a corresponding author on the paper.