Determination of the target proteins in chemotherapy resistant breast cancer stem cell-like cells by protein array.

ABSTRACT

Breast cancer comes second among the causes of cancer deaths of women. Although new generation hormone therapy is a promising strategy, re-occurrence or emergence of drug resistance limits the success. According to the theory of cancer stem cells (CSCs); CSCs are immortal, tumor inducing and self renewing pluripotent cells and multiply as chemotherapy proceeds, making the chemotherapy inefficient. Emerging scientific reports indicate that the mechanisms of drug resistance are the main features that CSCs gain actually. Due to this fact, cancer stem cell markers should be clarified to target CSCs and this will play important role to reverse drug resistance. In this study, MCF-7/Pac, a cell line resistant to microtubule inhibitor paclitaxel and multiple drugs permanently, was used as a reference cell line for drug resistant mammary cancer. It has some properties that breast cancer stem cells possess so it is considerable to isolate breast cancer stem cell-like cells from MCF-7/Pac population. The chemotherapy resistant breast cancer stem-like (BCSC-like) cells were sorted from MCF-7/Pac population by using markers CD44, CD24 and ALDH. At the next step the proteins that are up-regulated in BCSC-like cells were determined by protein array analysis. Additionally the effect of paclitaxel on BCSC-like cell proliferation was determined. The MCF-7/Pac population contains 12.4% BCSC-like cells. The cells bearing BCSC-like cell phenotype exhibited resistance to paclitaxel. The over-expressed growth factors, MMP proteins, Frizzled proteins and IL-23 were found to be related to the BCSC-like cell proliferation. These results will guide both basic science and medical science.