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

Wang J, Tran J, Wang H, Luo W, Guo C, Harro D, Campbell AD, Eitzman DT - Exp Hematol Oncol (2015)

Bottom Line: 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.Therapies targeting angiogenesis or HO-1 may be useful in SCD patients with malignant tumors.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Hemin induces HO-1 expression in cultured endothelial cells and promotes angiogenesis from aortic rings. a HO-1 expression level in bEend.3 cells treated with DMSO (control), 1 μM hemin or 5 μM hemin. b Quantification of sprouts from aortic rings treated with DMSO (control), 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. c Representative images of sprouts from aortic rings treated with DMSO, 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. Scale bar = 500 μm
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Fig3: Hemin induces HO-1 expression in cultured endothelial cells and promotes angiogenesis from aortic rings. a HO-1 expression level in bEend.3 cells treated with DMSO (control), 1 μM hemin or 5 μM hemin. b Quantification of sprouts from aortic rings treated with DMSO (control), 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. c Representative images of sprouts from aortic rings treated with DMSO, 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. Scale bar = 500 μm

Mentions: Hemin is elevated in SCD and has been shown to induce HO-1 [17]. To determine the effect of hemin on HO-1 induction in endothelial cells, hemin was incubated with endothelial cells in culture. Hemin induced a dose dependent increase of HO-1 expression in endothelial cells (Fig. 3a). To determine the angiogenic response to hemin, hemin was incubated with isolated aortic rings using an established aortic ring angiogenesis model [12]. Hemin increased the number of angiogenic sprouts (Fig. 3b and c). This effect was blocked with addition of ZnPP suggesting that hemin induced angiogenesis via HO-1.Fig. 3


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

Wang J, Tran J, Wang H, Luo W, Guo C, Harro D, Campbell AD, Eitzman DT - Exp Hematol Oncol (2015)

Hemin induces HO-1 expression in cultured endothelial cells and promotes angiogenesis from aortic rings. a HO-1 expression level in bEend.3 cells treated with DMSO (control), 1 μM hemin or 5 μM hemin. b Quantification of sprouts from aortic rings treated with DMSO (control), 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. c Representative images of sprouts from aortic rings treated with DMSO, 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. Scale bar = 500 μm
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4496890&req=5

Fig3: Hemin induces HO-1 expression in cultured endothelial cells and promotes angiogenesis from aortic rings. a HO-1 expression level in bEend.3 cells treated with DMSO (control), 1 μM hemin or 5 μM hemin. b Quantification of sprouts from aortic rings treated with DMSO (control), 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. c Representative images of sprouts from aortic rings treated with DMSO, 1 μM hemin or 1 μM hemin with 2.5 μM ZnPP. Scale bar = 500 μm
Mentions: Hemin is elevated in SCD and has been shown to induce HO-1 [17]. To determine the effect of hemin on HO-1 induction in endothelial cells, hemin was incubated with endothelial cells in culture. Hemin induced a dose dependent increase of HO-1 expression in endothelial cells (Fig. 3a). To determine the angiogenic response to hemin, hemin was incubated with isolated aortic rings using an established aortic ring angiogenesis model [12]. Hemin increased the number of angiogenic sprouts (Fig. 3b and c). This effect was blocked with addition of ZnPP suggesting that hemin induced angiogenesis via HO-1.Fig. 3

Bottom Line: 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.Therapies targeting angiogenesis or HO-1 may be useful in SCD patients with malignant tumors.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus