Accession Number:

ADA621812

Title:

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

Descriptive Note:

Annual rept. 1 Apr 2014-30 Mar 2015

Corporate Author:

VIRGINIA COMMONWEALTH UNIV RICHMOND

Personal Author(s):

• Avni, Dorit

Report Date:

2015-05-01

Pagination or Media Count:

13.0

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 ER-alpha expression and sensitize breast cancer cells to tamoxifen therapy.

Descriptors:

• *BREAST CANCER
• *OBESITY
• *PHOSPHORUS TRANSFERASES
• CELLS(BIOLOGY)
• CLINICAL MEDICINE
• CYTOKINES
• EXPERIMENTAL DESIGN
• GENE EXPRESSION
• GROWTH(PHYSIOLOGY)
• IMMUNOLOGY
• IN VIVO ANALYSIS
• INFLAMMATION
• LUNG CANCER
• MACROPHAGES
• MAMMARY GLANDS
• METASTASIS
• MICE
• NEOPLASMS
• PATHOPHYSIOLOGY
• PHYSIOLOGICAL EFFECTS
• RESPONSE(BIOLOGY)
• RISK
• THERAPY
• TISSUES(BIOLOGY)

Subject Categories:

• Biochemistry
• Genetic Engineering and Molecular Biology
• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE