Melanoma tumor growth is accelerated in a mouse model of sickle cell disease

Jintao Wang, Jennifer Tran, Hui Wang, Wei Luo, Chiao Guo, David Harro, Andrew D. Campbell, Daniel T. Eitzman

The effect of sickle cell disease (SCD) on tumor growth is unknown. Sickled red blood cells may form aggregates within the microvasculature of hypoxic tumors and reduce blood flow leading to impairment of tumor growth. However, there is a paucity of data related to tumor growth in SCD. To investigate the effect of SCD on tumor growth in a melanoma model, we generated SCD and control mice using bone marrow transplantation and inoculated the chest wall with B16-F10 melanoma cells. Tumor growth was monitored and angiogenesis was studied in vivo and in vitro. From day 1 to 21, tumor growth rate was nearly identical between SCD and WT mice, however from day 22 to day 29 tumor growth was accelerated in SCD mice compared to WT mice. Disparity in tumor size was confirmed at autopsy with an approximate 2-fold increase in tumor weights from SCD mice. Tumors from SCD mice showed increased vascularity and elevated levels of heme oxygenase-1 (HO-1). HO-1 inhibition with zinc protoporphyrin (ZnPP) blocked the angiogenic and tumor growth response to SCD in vivo and the response to hemin in vitro. Growth of melanoma tumors is potentiated in a mouse model of SCD. Therapies targeting angiogenesis or HO-1 may be useful in SCD patients with malignant tumors.