A naturally occurring protein inhibits tumor growth and metastasis into secondary organs and has the potential to be developed into an anticancer drug, scientists have found.
Other studies have shown that the body’s own blood plasma protein—histidine-rich glycoprotein, or HRG—can affect the growth of blood vessels in tumors. Now, Lena Claesson-Welsh, a professor in the immunology, genetics, and pathology department of Uppsala (Sweden) University, and colleagues now have demonstrated that HRG can transform a tumor’s inflammatory cells from the tumor-associated macrophages (TAMs) known as M2 macrophages, which promote tumor growth, to M1 macrophages, which can inhibit tumor growth and metastasis.
In their online report for Cancer Cell, the researchers described the chain of events revealed in their mouse studies: Tumors producing HRG grew more slowly and did not spread into subsidiary tumors. Tumor growth was inhibited when HRG downregulated the placenta growth factor (PIGF), an action that prompted M2 macrophages to transform to M1 macrophages. The M1 cells started an immune defense against the tumor, reducing its mass. Because the M1 macrophages also lacked the ability to stimulate the tumor’s blood vessels, the cancerous cells had a harder time getting through vascular walls to metastasize.
“Besides unveiling an important role for TAM polarization in tumor vessel abnormalization, and its regulation by HRG/PIGF, these findings offer therapeutic opportunities for anticancer and antiangiogenic treatment,” concluded the Claesson-Welsh team.