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Open Access 01-12-2014 | Research article

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

Authors: Sandra Burghoff, Xuan Gong, Claudia Viethen, Christoph Jacoby, Ulrich Flögel, Sabine Bongardt, Anne Schorr, Andreas Hippe, Bernhard Homey, Jürgen Schrader

Published in: BMC Cancer | Issue 1/2014

Abstract

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.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/898/prepub

Title: Growth and metastasis of B16-F10 melanoma cells is not critically dependent on host CD73 expression in mice
Authors: Sandra Burghoff
Xuan Gong
Claudia Viethen
Christoph Jacoby
Ulrich Flögel
Sabine Bongardt
Anne Schorr
Andreas Hippe
Bernhard Homey
Jürgen Schrader
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/1471-2407-14-898

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Background

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Conclusions

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