Abstract 1396: Response of primary culture of breast cancer to hypoxia and drug treatment

• Published in: Cancer research (Chicago, Ill.) Ill.), 2013-04, Vol.73 (8_Supplement), p.1396-1396
• Main Authors: Yin, Hong, Adegboyega, Patrick, Smith, Mylinh Smith, Glass, Jonathan
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-1396

Breast cancer is a heterogeneous disease. Several subtypes of breast cancer have been characterized and corresponding treatment strategies have been devised. However, outcomes are not always satisfactory for a variety of reasons including individual variation in age, race, disease stages, and genetic variations. In order to improve the outcomes of breast cancer treatment, personalized treatment has been developed based on molecular profiling and genetic testing of each individual patient. To compliment the development of personalized treatment based on molecular data from genetic profiling, we hypothesized that culture of primary breast cancer tissue could provide a cell-based model that could be utilized in the evaluation of the response of individual breast cancer to therapeutic agents. In this model, breast cancer samples were cultured in matrigel. To identify the cell types that grew in the matrigel, the cells were subjected to the staining with antibodies against cytokeratin5, cytokeratin14, cytokeratin18, ER, vimentin, E-cadherin, N-cadherin, α-SMA, and β-catenin. The results demonstrated that the cells which grew from breast cancer tissue were heterogeneous, including epithelial and stromal cells. Further analysis of the effect of oxygen indicated that the growth of breast cancer cells increased by 1.4-1.5 fold with 5% O2 compared to growth with 21% O2. Interestingly, hypoxia did not stimulate growth of normal breast tissue. Very intriguingly, growth under hypoxic conditions demonstrated differential responses to several chemotherapeutic agents. In these studies cell proliferation was assayed at 5% and 21% O2 of primary cultures of normal and cancerous breast cells treated with doxorubicin, LY294002, and PHA665752 (c-Met inhibitor). With doxorubicin treatment normal breast cells under hypoxia showed significant drug resistance at 0.1 μM and 1 μM compared to normoxia (P