Ferritin Favors Tumor Growth by Blocking an Inhibitor of New Blood Vessel Formation

Cancer researchers have found that the serum iron transport protein ferritin stimulates tumor growth and expansion by blocking the antiangiogenic activity of another blood protein, HKa (cleaved high molecular weight kininogen).

The current study was prompted by findings that ferritin levels were often elevated in cancer patients. "It has been known for a long time that levels of ferritin are increased in people with tumors, but it has never been understood why that happens," explained senior author Dr. Suzy V. Torti, associate professor of biochemistry at Wake Forest University (Winston-Salem, NC, USA). "Ferritin appears to play an important role in blood vessel formation. Further, the interaction between ferritin and HKa may represent a new area of interest for possible drug development."

The investigators worked with a line of immunocompromised mice into which they transplanted cells from human prostate tumors. They reported in the January 6, 2009, online edition of the journal the Proceedings of the [U.S.] National Academy of Sciences (PNAS) that ferritin bound to HKa with high affinity and that ferritin blocked the antiangiogenic effects of Hka. This interaction, which was independent of ferritin's iron content, enhanced the migration, assembly, and survival of HKa-treated endothelial cells. Peptide mapping revealed that ferritin bound to a 22-amino acid subdomain of HKa that was critical to its antiangiogenic activity.

In the mouse xenograft study, coinjection of Hka and cancer cells produced small tumors with inhibited blood vessel formation. However, addition of ferritin to the mixture of HKa and cancer cells restored blood vessel formation, promoting tumor growth.

"Blood vessels can either be helpful, for example in wound healing, or they can be harmful, for example by favoring tumor growth," said Dr. Torti. "Our new finding is that the interaction between ferritin and HKa can influence blood vessel formation. This finding could serve as the basis for strategies to either inhibit or stimulate blood vessels. This opens up a new realm of potential ways to treat tumors or other conditions that depend on new blood vessel formation."

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