Growth and metastasis of B16-F10 melanoma cells is not critically dependent on host CD73 expression in mice

BMC Cancer

Sandra Burghoff³  Xuan Gong¹  Claudia Viethen¹  Christoph Jacoby¹  Ulrich Flögel¹  Sabine Bongardt¹  Anne Schorr²  Andreas Hippe²  Bernhard Homey²  Jürgen Schrader¹ 

[1] Institute of Molecular Cardiology, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, Germany

[2] Department of Dermatology, University Hospital Duesseldorf, 40225 Duesseldorf, Germany

[3] Current address: MVZ Labor Dessau GmbH, 06847 Dessau, Germany

关键词: Mice;    Tumor;    Immune system;    Adenosine;    B16-F10 melanoma;    CD73;   

Others  :  1117973
DOI  :  10.1186/1471-2407-14-898

 received in 2014-03-31, accepted in 2014-11-27,  发布年份 2014

【 摘 要 】

Background

Recent studies have suggested that adenosine generated by ecto-5′-nucleotidase (CD73) in the tumor microenvironment plays a major role in promoting tumor growth by suppressing the immune response and stimulating angiogenesis via A2A and A2B receptors. However, adenosine has also been reported to inhibit tumor growth acting via A1 and A3 receptors. Therefore the aim of this study was to clarify the role of host CD73, which catalyzes the extracellular hydrolysis of AMP to adenosine, on tumor growth and metastasis of B16-F10 melanoma cells.

Methods

CD73 and alkaline phosphatase (AP) activity of B16-F10 melanoma cells were measured by HPLC. Tumor cells were injected either subcutaneously or intradermally in WT and CD73^−/− mice and tumor growth was monitored by MRI at 9.4 T. Immune cell subpopulations within tumors were assessed by FACS after enzymatic digestion. An endothelium specific CD73^−/− was created using Tie2-Cre⁺ mice and CD73^flox/flox (loxP) mice. Chimeric mice lacking CD73^−/− on hematopoietic cells was generated by bone marrow transplantation. Lung metastatic spread was measured after intravenous B16-F10 application.

Results

B16-F10 cells showed very little CD73 and negligible AP activity. Neither complete loss of host CD73 nor specific knockout of CD73 on endothelial cells or hematopoietic cells affected tumor growth after subcutaneous or intradermal tumor cell application. Only peritumoral edema formation was significantly attenuated in global CD73^−/− mice in the intradermal model. Immune cell composition revealed no differences in the different transgenic mice models. Also lung metastasis after intravenous B16-F10 injection was not altered in CD73^−/− mice.

Conclusions

CD73 expression on host cells, particularly on endothelial and hematopoietic cells, does not modulate tumor growth and metastatic spread of B16-F10 melanoma cells most likely because of insufficient adenosine formation by the tumor itself.

【 授权许可】

   
2014 Burghoff et al.; licensee BioMed Central Ltd.

【 图 表 】

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