title: Melanoma tumor growth is accelerated in a mouse model of sickle cell disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, 7301A MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0644 USA.
authors.forename: Jintao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tran
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, 7301A MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0644 USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, 7301A MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0644 USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, 7301A MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0644 USA.
authors.forename: Chiao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Chemical Pathology, University of Michigan Hospital, Ann Arbor, MI USA.
authors.forename: David
authors.initials: D
authors.lastname: Harro
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Campbell
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, 7301A MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0644 USA.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
keywords: Angiogenesis; Heme oxygenase-1; Melanoma; Sickle cell disease