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Int. J. Mol. Sci. 2017, 18(12), 2521; doi:10.3390/ijms18122521

Altered Leukocyte Sphingolipid Pathway in Breast Cancer

1
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlandia, Umuarama, Uberlandia, MG 38400-902, Brazil
2
Obstetric Division, Internal Medicine, University Hospital, Federal University of Uberlandia, Umuarama, Uberlandia, MG 38405-320, Brazil
3
Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
Received: 30 October 2017 / Revised: 15 November 2017 / Accepted: 17 November 2017 / Published: 24 November 2017
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

Sphingolipid metabolism pathway is essential in membrane homeostasis, and its dysfunction has been associated with favorable tumor microenvironment, disease progression, and chemotherapy resistance. Its major components have key functions on survival and proliferation, with opposing effects. We have profiled the components of the sphingolipid pathway on leukocytes of breast cancer (BC) patients undergoing chemotherapy treatment and without, including the five sphingosine 1-phosphate (S1P) receptors, the major functional genes, and cytokines, in order to better understand the S1P signaling in the immune cells of these patients. To the best of our knowledge, this is the first characterization of the sphingolipid pathway in whole blood of BC patients. Skewed gene profiles favoring high SPHK1 expression toward S1P production during BC development was observed, which was reversed by chemotherapy treatment, and reached similar levels to those found in healthy donors. Such levels were also correlated with high levels of TNF-α. Our data revealed an important role of the sphingolipid pathway in immune cells in BC with skewed signaling of S1P receptors, which favored cancer development even under chemotherapy, and may probably be a trigger of cancer resistance. Thus, these molecules must be considered as a target pathway for combined BC therapeutics. View Full-Text
Keywords: sphingosine 1-phosphate (S1P); sphingolipids; S1P receptors; breast cancer; leukocytes sphingosine 1-phosphate (S1P); sphingolipids; S1P receptors; breast cancer; leukocytes
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Maia, L.P.; Santos, P.S.; Alves, P.T.; Rodrigues, C.M.; Araújo, T.G.; Maia, Y.C.P.; Câmara, A.T.F.; Santos, D.W.; Goulart, L.R. Altered Leukocyte Sphingolipid Pathway in Breast Cancer. Int. J. Mol. Sci. 2017, 18, 2521.

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