Correlation of Cancer Stem Cell Markers ITGA6 and ALDH1 with Mammosphere Formation in Breast Cancer


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Kristin Manor1,Simon Timbrell2,Robert Clarke3,Nigel Bundred2
1University of Manchester,2University Hospital of South Manchester,3Manchester Breast Centre, Division of Cancer Sciences, University of Manchester

Abstract

Background

Cancer stem cell (CSC) theory identifies tumorigenic stem cells as the conduit for driving the progression of breast malignancies. Evidence of CSC propagation is reinforced by deriving mammospheres from breast tumour stem-like cells utilising non-adherent medium. This study aimed to substantiate a correlation between mammosphere activity and expression of well-established CSC markers, integrin alpha-6 (ITGA6) and aldehyde dehydrogenase (ALDH1); characterising this relationship will help guide clinical trials and future studies.

Method

We utilised 74 individual tumour samples with known mammosphere formation from previous studies. Anti-ITGA6 (Atlas, HPA012696) was used to measure the expression of ITGA6 with immunohistochemistry, and ALDH1 was measured with immunofluorescence using anti-ALDH1 (BD Biosciences, 611195). Mammosphere forming efficiency (MFE) was correlated to expression of ITGA6 and ALDH1 to identify patterns of association; correlation was evaluated by cell population, molecular and histological characteristics, recurrence and prognosis.

Results

We found no correlation between mammosphere activity and CSC markers ITGA6 (P = 0.808) or ALDH1 (P = 0.285). ALDH1 was observed only in HER2- invasive ductal carcinoma and did not correlate to MFE (P = 0.20; P = 0.285). Further analysis of ITGA6 by histological subtype (ILC: P = 0.614; IDC: P = 0.519), molecular phenotype (Luminal A: P = 0.942; Luminal B: P = 0.935; HER2+: P = 0.155; Triple Negative: P = 0.947); recurrence (yes: P = 0.786; no: P = 0.429) and prognosis (poor: P = 0.134; moderate: P = 0.299; good: P = 0.155) did not corroborate relationships between CSC expression and MFE.

Conclusion

While ITGA6 and ALDH1 are well-established CSC markers, patterns of association with MFE were not observed. Our results may indicate that these CSC markers are not essential for mammosphere formation, and further work regarding mammoshere-initiating cells and self-renewal is required to identify a therapeutically significant panel of CSC markers to guide clinical trials.