Anemia is a common complication of lung cancer, and is associated with morbidity and mortality. Anemia of cancer (AC) likely has mechanistic similarities to the anemia of inflammation, but the roles of hepcidin and other mediators in the development of AC have yet to be elucidated. BMP6 is a known positive regulator of hepcidin expression, but its role in AC has never been studied.
We created two mouse models of lung cancer using the syngeneic lung cancer cell lines TC-1 and LLC. C57/Bl6 mice were injected intraperitoneally with TC-1, LLC, or PBS, and sacrificed on days 7, 14, and 21 with specimens collected for hemoglobin, hepcidin mRNA, and Id1 mRNA (a marker of BMP6 activity).
By day 14, the TC-1 and LLC mice were more anemic than the control mice (p = 0.004, < 0.001, respectively). Liver median hepcidin measurements were significantly different by day 14. The TC-1 mice had higher hepcidin levels than the control mice with a trend towards significance (p = 0.052), but the LLC mice had lower hepcidin levels than both the control and TC-1 mice (p < 0.001). Both TC-1 and LLC mice displayed a direct and positive relationship between the hgb and the hepcidin level. Hepcidin levels also correlated with Id1 levels.
We created two mouse models of anemia of lung cancer. The TC-1 mice have inappropriately elevated hepcidin at day 14 despite the presence of significant anemia, indicating that hepcidin likely causes the iron restriction. LLC mice, by contrast, have suppressed hepcidin production. However, since the severity of anemia still correlates with hepcidin, the LLC model likely represent a later, more severe, form of AC where anemic suppression of hepcidin outweighs the regulation by the BMP pathway. The correlations between the hemoglobin and hepcidin level, and the Id1 level and hepcidin level indicate a key role for BMP6 in the anemia of lung cancer.
By identifying key mediators in the mechanism of anemia of lung cancer, we can begin developing therapeutic targets.
Airie Kim, No Financial Disclosure Information; No Product/Research Disclosure Information