Abstract B15: Development of an innovative treatment for obesity-related triple-negative breast cancer
Authors: Harmon Tia , Lanier Viola , Harbuzariu Adriana , Yang Lily , Gonzalez-Perez Ruben R. 
Published: May 2016

Background: Breast cancer is the second leading cause of cancer deaths in women in the US. Although Caucasian women have an increased risk of developing breast cancer, more African American women die from this disease. Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer which comprises ~18 % of breast cancer cases and is characterized by the lack of expression of the estrogen receptor (ER), progesterone receptor (PgR), and the human epidermal growth factor receptor B2 (Her2). Due to the lack of receptor expression there is no targeted therapy for this more aggressive form of breast cancer mainly affecting women under the age of 50, minorities, and those with a BRCA1 gene mutation. There are several risk factors for breast cancer, notably being overweight or obese. Obesity is associated with high levels of leptin, a cytokine produced by adipose tissue. Leptin upregulates Notch, interleukin 1 (IL-1), vascular endothelial growth factor (VEGF), and its receptor VEGFR2 which promote survival and angiogenesis. Leptin induces expression of Notch and VEGFR2 via the activation of the JAK2/STAT3 pathway. We have developed leptin peptide receptor antagonists linked to Iron Oxide Nanoparticles (IONP-LPrA2). IONP-LPrA2 has been shown to inhibit leptin signaling and decrease expression of its targets in cancer cells.

Methods: Human breast cancer cells were cultured in MEM with 10% fetal bovine serum and maintained in an incubator at 37⁰C with 5% CO2. Cells were cultured in 6 well culture plates and grown to 70-80% confluence. They were then treated with leptin and IONP-LPrA2. Subsequently, the cells were analyzed for leptin target expression with the Cellometer Vision Image Cytometer ® and by Immunoblotting analysis.

Results: IONP-LPrA2 was shown to abrogate leptin-induced JAK2/STAT3, Notch 1, and VEGFR2 expression in the breast cancer cell lines.

Conclusion: IONP-LPrA2 inhibits leptin signaling and decreases expression of leptin-induced target proteins. This data suggests that IONP-LPrA2 may serve as a treatment for breast cancer patients by minimizing the harmful effects of leptin signaling. IONP-LPrA2 may also act as a targeted therapy for those suffering from TNBC.

Acknowledgements: This work was partially supported by the DOD W81XWH-13-1-0382; NIH/SBIR 1R41CA183399-01A1; Pilot Project Award from MSM/Tuskegee University/UAB Cancer Center Partnership grant 5U54CA118638; PC SPORE Grant from UAB to RRGP, and facilities and support services at Morehouse School of Medicine (1G12RR026250-03; NIH RR03034 and 1C06 RR18386).

Citation Format: Tia Harmon, Viola Lanier, Adriana Harbuzariu, Lily Yang, Ruben R. Gonzalez-Perez. Development of an innovative treatment for obesity-related triple-negative breast cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B15.