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.
Highlights
Cancer is characterized by the accumulation of genetic and cellular alterations, which generate immune response to tumor antigens [1]
This study showed that sphingosine 1-phosphate receptors (S1PR) are expressed in lymphocytes, monocytes and granulocytes of breast cancer (BC) and BC patients undergoing chemotherapy treatment (BCC) patients at different levels
The analysis of T lymphocytes revealed that all S1PRs were more expressed in BCC group, whereas in granulocytes the higher levels of these receptors were observed in BC patients
Summary
Cancer is characterized by the accumulation of genetic and cellular alterations, which generate immune response to tumor antigens [1]. Effective responses against cancer cells depend on several steps, including tumor antigens capture by dendritic cells and presentation to T cells, which are activated. Effector T cells traffic and infiltrate in the tumor bed, recognize and bind to cancer cells, and kill them [2,3]. Monocytes are recruited to tumor tissues and differentiate into tumor-associated macrophages, performing pro-tumor functions with increased production of factors that support tumor initiation, neoplastic transformation, and distant metastasis onset [5,6]. Neutrophils are recruited and differentiate into tumor-associated neutrophils (TANs), but their functions are unclear, since TANs produce pro-inflammatory and anti-inflammatory factors [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
