Accession Number : ADA636997


Title :   Targeting Sphingosine-1-Phosphate Axis in Obesity-Promoted Breast Cancer


Descriptive Note : Annual rept. 1 may 2015-30 Apr 2016


Corporate Author : VIRGINIA COMMONWEALTH UNIV RICHMOND


Personal Author(s) : Avni, Dorit


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a636997.pdf


Report Date : 01 May 2016


Pagination or Media Count : 14


Abstract : Obesity, which induces low-grade inflammation, is a known risk factor for worse prognosis in many cancers including breast. We found that sphingosine-1-phosphate (S1P) produced by sphingosine kinases (SphKs) plays a critical role in obesity-related inflammation and breast cancer. Obesity increased S1P in the tumor microenvironment, as well as in the primary tumors. FTY720, a functional antagonist of S1PR1, dramatically decreased cancer progression by reducing expressions of SphK1 and S1PR1, and inflammatory cytokines including IL-6. Our results suggest a critical role for S1P in obesity-related inflammation and FTY720, an S1P axis inhibitor, appears to be a promising treatment for breast cancer in the obese condition, could be due to its effect on reactivate ERa expression and sensitize breast cancer cells to tamoxifen therapy.


Descriptors :   *BREAST CANCER , *OBESITY , CELLS(BIOLOGY) , CYTOKINES , GROWTH(PHYSIOLOGY) , INFLAMMATION , MACROPHAGES , MAMMARY GLANDS , METASTASIS , NEOPLASMS , PHOSPHORUS TRANSFERASES , PREDICTIONS , RISK , TARGETING


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE