Waleed Kholosy
University of Aberdeen, UK
Posters-Accepted Abstracts: J Cancer Sci Ther
Introduction: Cancers stem cells (CSC) are resistant cancer phenotype. This may be due to a defensive mechanism in order to survive under hypoxic conditions within niches with low ROS and confer chemo-resistance. CSC defensive mechanism may include increased expression of endogenous antioxidant systems, regulation of hypoxia responsive signaling and efflux transporter systems to protect the CSC from oxidative damage. Here, we examine the relationship between key endogenous antioxidants (Prx-I and Trx-1), CSC transporter protein (ABCG2), a hypoxia marker (HIF-1���±) and a potential breast CSC marker (ALDH1A3) in breast cancer stem cell niches using clinical resections tissue micro arrays. Methods: Using immunohistochemistry (IHC), 556 breast tumor specimens in formalin fixed paraffin blocks were used to construct tissue microarrays (TMA) from 556 patients recruited to two different breast cancer studies (MoBCaT and BREACAST). The following markers Prx-I, Trx-1, HIF-1���±, ABCG2 and ALDH1A3 were evaluated by IHC. The relationships between these markers and the histopathological parameters of the tumor and clinical characteristics of patients were analyzed. Results: High expression of Prx-I and Trx-1 were associated with poor prognostic markers including high grade, worse NPI status and higher tumor stage. Prx-1 and stromal Trx-1 showed an association with 5-year patient survival (p=0.04; p=0.011). High levels of Trx-1 were correlated with high Prx-I expression. There were correlations between ABCG2 and each of the markers investigated. However, no association was found between these markers and ALDH1A3+tumors. Conclusion: Prx-I and stromal Trx-1 are associated with patient survival and can be used as prognostic markers in breast cancer. ABCG2 expression is associated with other markers investigated in this study. These relationships may be reflections of the concerted protective mechanisms in which tumor cells over express anti-oxidant response, hypoxia related proteins and efflux pumps to reduce ROS levels and prevent further damage within breast CSC microenvironment.
Email: w.m.k.hassan@student.rug.nl
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