Abstract 4629: The influence of adipose tissue-derived mesenchymal stem cell environment and WNT antagonism on breast tumour cells
Authors: Visweswaran Malini , Arfuso Frank , Dilley Rodney , Newsholme Philip , Dharmarajan Arunasalam 
Published: July 2016

Breast cancer is the most commonly diagnosed cancer in Australian women, with an average of 1 in 8 women being affected. Emerging evidence suggests that a close relationship exists between a tumor and the adjacent non-tumor tissue, which considerably affects the overall progression of the disease. Amongst the non-tumor cells, mesenchymal stem cells (MSCs), known to be essential for tissue and organ health, are potentially important in this regard. In our study, we focussed on the interaction between adipose tissue-derived MSCs (ADSCs) and breast tumor cells. Considering the clinical relevance of these interactions, it is imperative to understand the exact mechanisms underlying such cellular crosstalk. Here, we investigated the influence of ADSCs on breast tumor cell lines MDA MB 231 and MCF7 by using both conditioned media and extracellular matrix derived from ADSCs. We observed that the ADSC-conditioned media (ADSC-CM), harvested at specific time-points, inhibited the proliferation of tumor cells as well as their associated cancer stem cells. Further, by using molecular fractionation techniques on ADSC-CM, we identified that the &lt;30KDa fraction of ADSC-CM retained the potential for inhibiting proliferation. We also observed decreased migration of tumor cells when treated with ADSC-CM. Further, we observed an inhibition in proliferation rates of tumor cells when treated with ADSC-deposited extracellular matrix (ADSC-ECM). Since Wnt signaling is an important pathway driving both breast tumor growth and influencing ADSC behaviour, we examined the effect of the Wnt antagonist- secreted frizzled-related protein 4 (sFRP4) and its associated peptides on tumor cells. When tumor cells were treated with sFRP4 or its peptides along with ADSC-CM/ADSC-ECM, we observed an additive inhibitory effect on tumor cell proliferation. We further observed an increase in caspase-dependent apoptosis in tumor cells following treatment with ADSC-CM and in combination with the Wnt antagonists. The effect contributed by the ADSC environment and Wnt antagonists differed in mechanism, based on the tumor cell characteristics. We can conclude that the interaction of ADSCs with tumor cells had a significant impact on tumor cell growth in terms of decreasing proliferation and migration, while increasing the rate of apoptosis, which was further elevated in the presence of Wnt antagonists. This study sheds light on novel therapeutic approaches that could be considered while devising novel anti-cancer strategies.

Citation Format: Malini Visweswaran, Frank Arfuso, Rodney Dilley, Philip Newsholme, Arunasalam Dharmarajan. The influence of adipose tissue-derived mesenchymal stem cell environment and WNT antagonism on breast tumour cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4629.