Caracterização molecular e imunológica da via dos esfingolipídios em tecido tumoral e em células do sistema imune no câncer de mama

Abstract

The present study investigated the effects of the sphingolipid pathway on breast cancer (BC) immunity, analyzing receptors, the major functional genes of the pathway and cytokines to characterize the involvement of the sphingosine 1-phosphate (S1P) signaling in the immunological response of breast cancer. To the best of our knowledge, there is no characterization of the sphingolipid pathway in whole blood from breast cancer patients in literature. This study demonstrates a skewed profile of genes favoring high SPHK1 expression and production of S1P in tissues and blood during BC development, which was reversed by chemotherapy treatment (BCC) and reached levels similar to those found in benign disease. Such levels were also correlated with high levels of pro-inflammatory cytokines. This study also shows for the first time the characterization of all five S1P receptors in lymphocytes, granulocytes and monocytes from both BC and BCC patients. Although cells express all five receptors, they vary in their surface expression, and this differential expression seem to play major roles in the tumor immune system that may lead to immune evasion, cell infiltration, proliferation, survival and dissemination.