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

被引：7
作者：
Wang J. [1 ]
Tran J. [2 ]
Wang H. [1 ]
Luo W. [1 ]
Guo C. [1 ]
Harro D. [3 ]
Campbell A.D. [2 ]
Eitzman D.T. [1 ]
机构：
[1] University of Michigan, Department of Internal Medicine, Cardiovascular Research Center, 7301A MSRB III, 1150 West Medical Center Drive, Ann Arbor, 48109-0644, MI
[2] University of Michigan, Department of Pediatrics, Ann Arbor, MI
[3] University of Michigan Hospital, Chemical Pathology, Ann Arbor, MI
来源：
Experimental Hematology & Oncology | / 4卷 / 1期
基金：
美国国家卫生研究院;
关键词：
Angiogenesis; Heme oxygenase-1; Melanoma; Sickle cell disease;
D O I：
10.1186/s40164-015-0014-1
中图分类号：
学科分类号：
摘要：
Background: 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. Methods: 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. Results: 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. Conclusions: 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. © 2015 Wang et al.
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  • [1] Vaupel P., Kallinowski F., Okunieff P., Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review, Cancer Res, 49, 23, pp. 6449-6465, (1989)
  • [2] Terman D.S., Viglianti B.L., Zennadi R., Fels D., Boruta R.J., Yuan H., Dreher M.R., Grant G., Rabbani Z.N., Moon E., Et al., Sickle erythrocytes target cytotoxics to hypoxic tumor microvessels and potentiate a tumoricidal response, PloS one, 8, 1, (2013)
  • [3] Wang H., Luo W., Wang J., Guo C., Wolffe S.L., Wang J., Sun E.B., Bradley K.N., Campbell A.D., Eitzman D.T., Paradoxical protection from atherosclerosis and thrombosis in a mouse model of sickle cell disease, Br. J. Haematol., 162, 1, pp. 120-129, (2013)
  • [4] Was H., Cichon T., Smolarczyk R., Rudnicka D., Stopa M., Chevalier C., Leger J.J., Lackowska B., Grochot A., Bojkowska K., Et al., Overexpression of heme oxygenase-1 in murine melanoma: increased proliferation and viability of tumor cells, decreased survival of mice, Am. J. Pathol., 169, 6, pp. 2181-2198, (2006)
  • [5] Duits A.J., Rodriguez T., Schnog J.J., Group C.S., Serum levels of angiogenic factors indicate a pro-angiogenic state in adults with sickle cell disease, Br. J. Haematol., 134, 1, pp. 116-119, (2006)
  • [6] Mund J.A., Shannon H., Sinn A.L., Cai S., Wang H., Pradhan K.R., Pollok K.E., Case J., Human proangiogenic circulating hematopoietic stem and progenitor cells promote tumor growth in an orthotopic melanoma xenograft model, Angiogenesis, 16, 4, pp. 953-962, (2013)
  • [7] Wu L.C., Sun C.W., Ryan T.M., Pawlik K.M., Ren J., Townes T.M., Correction of sickle cell disease by homologous recombination in embryonic stem cells, Blood, 108, 4, pp. 1183-1188, (2006)
  • [8] Campbell A.D., Cui S., Shi L., Urbonya R., Mathias A., Bradley K., Bonsu K.O., Douglas R.R., Halford B., Schmidt L., Et al., Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes, Proc. Natl. Acad. Sci. U. S. A., 108, 46, pp. 18808-18813, (2011)
  • [9] Xia S., Lu Y., Wang J., He C., Hong S., Serhan C.N., Kang J.X., Melanoma growth is reduced in fat-1 transgenic mice: impact of omega-6/omega-3 essential fatty acids, Proc. Natl. Acad. Sci. U. S. A., 103, 33, pp. 12499-12504, (2006)
  • [10] Weidner N., Semple J.P., Welch W.R., Folkman J., Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma, N. Engl. J. Med., 324, 1, pp. 1-8, (1991)
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