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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

Accelerated tumor growth in SCD mice. a Growth curves of WT mice (n = 10) and SCD mice (n = 10). b Representative image of tumor bearing SCD and WT mouse at time of sacrifice. c Tumor weights of WT and SCD mice at time of sacrifice. d Sickled erythrocytes within tumor vessels from SCD mice. Scale bar = 25 μm
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Fig1: Accelerated tumor growth in SCD mice. a Growth curves of WT mice (n = 10) and SCD mice (n = 10). b Representative image of tumor bearing SCD and WT mouse at time of sacrifice. c Tumor weights of WT and SCD mice at time of sacrifice. d Sickled erythrocytes within tumor vessels from SCD mice. Scale bar = 25 μm

Mentions: To determine the effect of SCD on the growth of malignant tumors, we implanted murine melanoma cells in SCD and WT recipients. Tumors were implanted over the left lateral chest wall so that they could be easily monitored and measured daily. Growth of tumors during the first 3 weeks was similar between the WT and SCD mice (Fig. 1a). From day 21 to 29, there was acceleration of tumor growth rate in both groups but the rate of growth was markedly increased in the SCD group compared to the WT group (Fig. 1a). Tumor volumes and weights were both increased in the SCD compared to WT mice at time of sacrifice (Fig. 1a, b, c). Body weights of mice at the beginning and end of the protocol were similar between the WT and SCD mice (24.93 ± 1.13 vs. 24.03 ± 0.79 grams on day 1; 25.46 ± 0.79 vs 25.74 ± 1.22 grams on day 29). Histological analyses showed frequent microvascular occlusions in tumors from SCD mice (Fig. 1d). Visible metastatic lung surface nodules were present in 40 % of wild-type mice and 55 % of SCD mice at the time of sacrifice. However, there was no significant difference between the two groups (p value for Fisher’s exact test = 0.67).Fig. 1


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)

Accelerated tumor growth in SCD mice. a Growth curves of WT mice (n = 10) and SCD mice (n = 10). b Representative image of tumor bearing SCD and WT mouse at time of sacrifice. c Tumor weights of WT and SCD mice at time of sacrifice. d Sickled erythrocytes within tumor vessels from SCD mice. Scale bar = 25 μm
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig1: Accelerated tumor growth in SCD mice. a Growth curves of WT mice (n = 10) and SCD mice (n = 10). b Representative image of tumor bearing SCD and WT mouse at time of sacrifice. c Tumor weights of WT and SCD mice at time of sacrifice. d Sickled erythrocytes within tumor vessels from SCD mice. Scale bar = 25 μm
Mentions: To determine the effect of SCD on the growth of malignant tumors, we implanted murine melanoma cells in SCD and WT recipients. Tumors were implanted over the left lateral chest wall so that they could be easily monitored and measured daily. Growth of tumors during the first 3 weeks was similar between the WT and SCD mice (Fig. 1a). From day 21 to 29, there was acceleration of tumor growth rate in both groups but the rate of growth was markedly increased in the SCD group compared to the WT group (Fig. 1a). Tumor volumes and weights were both increased in the SCD compared to WT mice at time of sacrifice (Fig. 1a, b, c). Body weights of mice at the beginning and end of the protocol were similar between the WT and SCD mice (24.93 ± 1.13 vs. 24.03 ± 0.79 grams on day 1; 25.46 ± 0.79 vs 25.74 ± 1.22 grams on day 29). Histological analyses showed frequent microvascular occlusions in tumors from SCD mice (Fig. 1d). Visible metastatic lung surface nodules were present in 40 % of wild-type mice and 55 % of SCD mice at the time of sacrifice. However, there was no significant difference between the two groups (p value for Fisher’s exact test = 0.67).Fig. 1

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