Abstract PL03-03: Differences in breast cancer stem cell signaling and metabolic integration associated with African versus European ancestry

In the US where extensive studies have been conducted, African-American(AA) women have poorer survival from breast cancer (BC) even after adjusting for stage, age, treatment and co-morbid conditions. Since survival in BC is mainly dependent on the appearance and robustness of metastasis, we have hypothesized that BC occurring in women with African ancestry have a greater metastatic potential. With the growing evidence that BC tumor initiation, metastases and recurrence is driven by stem-like cancer cells, we further hypothesize that BC in women of African descent has aggressive phenotypic characteristics that result from the integration of signaling alterations and metabolic adaptations in their cancer stem cells. Rodent xenograft models are powerful tools for studying tumor biology and treatment response to novel agents, but they are challenging to develop in the laboratory. Here we describe the first-ever creation of a library of xenografts from a series of patients affected with triple negative breast cancer (TNBC) from sub-Saharan Africa, based upon a unique international collaboration; we also report on studies that are being conducted on the xenografts to understand the stem cell biology of aggressive African breast cancers. Methods: Our research team explored several different strategies for obtaining fresh tumor specimens from Ghanaian patients with aggressive TNBC tumors, undergoing surgery in Kumasi, Ghana, and rapidly transporting these tissues for implantation into immunocompromised mice in the United States. Xenograft tumors were also developed from AA and Caucasian American (CA) patients undergoing surgery in the United States. The whole genome expression patterns of the bulk tumor as well as the stem cell compartments were compared for AA, Ghanaian and CA TNBC. Single cells from the tumors were grown in suspension and in attachment plates. Results: Successful xenografts were created by harvesting fresh tissue from patients undergoing surgery in Ghana, slow freezing tumor pieces at -80o C and transporting it on dry ice by air to the United States within 24-36 hours to implant into nod scid gamma mice. Currently we have successful growth, as follows: 12 tumors from 4 patients growing in 10 mice. We have successful growth of tumorspheres and cell lines from single cells separated from the xenografts, as additional resources for biological studies of signaling and metastases. In a preliminary study, we have performed a gene array expression study of AA and White American triple negative and estrogen positive cell lines that show significantly different gene expression patterns, with the cell lines of high African ancestry segregating from Caucasian cell lines . Conclusions: The study of aggressive breast cancers in African populations is feasible through the creation of xenografts from fresh tumor tissue harvested from the treating facilities and transported to laboratories in the United States. International collaborations are critical for this process and should thus be encouraged, to create the appropriate resources worldwide to improve our understanding of aggressive BC subtypes.. Moreover, we are finding common expression patterns in TNBC of African extraction. This will help advance our understanding of the survival disparities. To this end, we will be able to test the observed differences in the new tumorspheres and cell lines developed directly from patients. Citation Format: Evelyn M. Jiagge, Jessica Bensenhaver, Sean McDermott, Awuah Baffour, Max Wicha, Lisa A. Newman, Sofia Merajver. Differences in breast cancer stem cell signaling and metabolic integration associated with African versus European ancestry. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr PL03-03. doi:10.1158/1538-7755.DISP13-PL03-03