ABCG2 as a potential cancer stem cell marker in breast cancer.

Abstract

e12007 Background: The identification of cancer stem cell (CSC) markers gives opportunity to develop new target therapies. ABCG2 protein is reported as a predictive marker for breast cancer resistance to chemotherapy and as a potential marker for CSC in solid tumors. Methods: We included prospectively 41 patients with locally advanced or metastatic (LAMBC) invasive ductal carcinomas treated with NACT. The expression of CD44/CD24 and ABCG2 was analyzed by flow cytometry after fresh tumor sample digestion. The mammosphere assay (Mammocult) was carried out in 23 samples. We analyzed the correlation between the percentage of ESA+/ABCG2+ and ESA+/CD44+/CD24- cells within the primary tumor with the number of spheres in culture and their relationship with clinical and pathological parameters. ABCG2+ and ABCG2- cells from four primary tumors and from MDA-MB231 cell line were sorted and cultured in triplicate in Mammocult medium for 7 days. The ability to form sphere was analyzed. Patients’ mean age was 52.8 ± 10.3 yo. The ER, PgR and HER2 positive expression rates were 65%, 58% and 45%, respectively. Patients were treated with docetaxel/anthracycline combination (n = 33) of FEC75 combination (n = 8). Results: Complete pathological response was observed in 10 patients (24%). ER negative patients and patients with lower percentage of ABCG2+ cells within the tumor were more likely to achieve near pCR (44% versus 11%, p = 0.04; and 50% versus 14%, p = 0.04, respectively). We did not observe a significant association between pCR and PgR and HER2 expression or the percentage of CD44+/CD24- cells within the tumor. There was a strong correlation between the percentage of ESA+/ABCG2+ cells and the number of mammospheres in culture (r = 0.63; p= 0.0007). This correlation was not significant comparing to CD44+/CD24- cells. Additionally, ABCG2+ cells from primary tumors and MB-231 cell line form a higher number of spheres in culture than ABCG2- (mean difference = 1.15±0.45 /1000 cells, p = 0.04; mean difference = 0.48±0.04 /1000cells, p = 0.008, respectively). Conclusions: ABCG2 is a potential marker for CSC in breast cancer, and the percentage of ABCG2+ cancer cells within the tumor is a predictive factor for pCR in LAMBC patients subjected to NACT.

Counteracting Chemoresistance with Metformin in Breast Cancers: Targeting Cancer Stem Cells

“…BCSCs reportedly overexpress the ATP binding cassette (ABC) transporters such as the ABCB1/multi-drug resistance protein-1 (MDR1)/P-gp, ABC sub-family G-2 (ABCG2)/breast cancer resistance protein (BCRP), ABC sub-family C-1 (ABCC1)/multidrug resistance-associated protein 1 (MRP1), ABC sub-family C-3 (ABCC3), and ATP-binding cassette sub-family B-5 (ABCB5), all of which were implicated in the ability of BCSCs to resist drug interventions and trigger cancer relapse [ 185 ]. ABCG2/BCRP and ABCB1/MDR1/P-gp that efflux Hoechst 33342 dye are also used as a function of cell surface markers for chemoresistance in BCSCs [ 186 , 187 ].…”

Machine Learning Model for Prediction of Development of Cancer Stem Cell Subpopulation in Tumurs Subjected to Polystyrene Nanoparticles

“…In addition, studies have shown the functional relevance of ATP binding cassette subfamily G member 2 -ABCG2 (also known as BCRP, a breast cancer resistance protein) in relation to CSCs and therapeutic response. ABCG2 has been identified as a predictive marker of chemotherapy resistance and a potential CSC marker in solid tumors [5]. Resistance to cytotoxic agents has been attributed to the efflux of chemotherapeutic drugs by CSC-expressed ABCG2 [6].…”

Heterogeneity beyond tumor heterogeneity—SULF2 involvement in Wnt/β-catenin signaling activation in a heterogeneous side population of liver cancer cells

“…SP cells have shown functions different from those of NSP cells and have been considered a substitute for CSCs, to some extent, in several studies (Dubrovska et al, 2012;Feng et al, 2015;Guo et al, 2016;Liao et al, 2015;Summer et al, 2003;Teshima et al, 2014;Van den Broeck et al, 2013;Wang et al, 2017;Zhao et al, 2016). Isolation of SP cells is typically based on their ability to pump out Hoechst 33342 dye given the high expression of adenosine triphosphate (ATP)-binding cassette (ABC) membrane transporters on their membranes (27, 28 Goodell, 2005;Patrawala et al, 2005), a characteristic of stem cells (Ding et al, 2010;Hu et al, 2017;Tiezzi et al, 2013). Further, SP cells cannot pump out Hoechst 33342 dye when verapamil, a calcium channel antagonist, is used to inhibit ABC membrane transporters, whereas the influence of verapamil on NSP cells is negligible (Scharenberg et al, 2002).…”