Role of shNDPK and E-Cadherin in Growth and Metastasis of an Inflammatory Breast Cancer Model (MARY-X)

Abstract

MARY-X, an inflammatory breast cancer (IBC) murine xenograft, exhibits the formation of florid lymphovascular emboli in vivo and spheroid formation in vitro. IBC is highly invasive and metastatic and our model presents the same in mice as it does in human. Therefore, studying the molecular processes involved in this IBC murine model will allow us to uncover the mechanisms promoting cancer growth and metastasis of IBC specifically and cancer in general. In this study we determined the extracellular expression of secreted NDPK in mice implanted with the MARY-X tumor as well as intracellular expression of NDPK in the MARY-X tumor cells. NDPK, which regenerates ATP, acts as an pro-angiogenic factor. NDPK promotes tumor growth by inducing endothelial cell proliferation. E-Cadherin, an adherence protein, is overexpressed in MARY-X spheroids and is responsible for the densely aggregated configuration and the stem cell-like nature of the in vivo emboli and the in vitro spheroids. We will also investigate specific E-Cadherin expression within MARY-X spheroids in order to identify the role of the unique expression of E-Cadherin in the stem cell-like nature of the MARY-X spheroids. These findings may uncover potential drug targets against IBC allowing development of more effective treatments preventing the growth and metastasis of IBC and other cancers.