A collaborative team of researchers including scientists from the School of Veterinary Medicine and Perelman School of Medicine show how a modified peptide can successfully target the immunosuppressive tumor microenvironment. (Image: iStock/Marcin Klapczynski)
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.
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