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Effects of Eribulin on Epithelial-Mesenchymal Plasticity in Patient-Derived Breast Cancer Cultures and Excised
Charles L Bidgood1,2, Erika Morera1,2,3, Binny Jaradi1,2
1Centre for Genomics and Personalised Health, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4059, Australia.
Background:
The cytotoxic agent eribulin has been shown to promote EMT reversion, reduce treatment resistance, and potentially enhance responses to a range of therapeutic agents.
Methods:
We examined the effects of eribulin in patient-derived breast cancer tissues and a phenotypically heterogeneous breast cancer cell line to assess EMT and chemotherapy response.
Results:
Nanostring-based analysis of EMT-associated gene expression in breast cancers from patients receiving standard-of-care TAC neoadjuvant chemotherapy compared to a cohort receiving neoadjuvant eribulin (NeoEribulin trial) showed markedly reduced expression of EMT markers in cancers treated with eribulin versus TAC. Through single-cell immunofluorescent imaging and analysis, we identified that HCC38 triple-negative breast cancer (TNBC) cells exhibited a shift towards an epithelial-like state marked by E-cadherin upregulation following acute eribulin exposure, but not with other chemotherapeutic agents. Investigation of primary breast cancer cultures derived from pre-neoadjuvant biopsies also revealed that HER2-enriched primary breast cancer cells displayed heightened chemosensitisation to doxorubicin (Adriamycin), which was not recapitulated in TNBC cultures.
Conclusions:
Our data highlight the presence of contextual parameters which govern the degree of EMT regulation by eribulin.
