Human-specific RNA analysis shows uncoupled epithelial-mesenchymal plasticity in circulating and disseminated tumour cells from human breast cancer xenografts
Anthony Tachtsidis, Anh Viet-Phuong Le, Tony Blick, Devika Gunasinghe, Emma De Sousa, Mark Waltham, Alex Dobrovic, Erik W Thompson
CLINICAL & EXPERIMENTAL METASTASIS | SPRINGER | Published : 2019
Blood samples, bone marrow, tumours and metastases where possible were collected from SCID mice bearing orthotopic xenografts of the triple-negative MDA-MB-468 cell line or a transplantable ER-positive patient derived xenograft (ED-03), and assessed using human-specific, tandem-nested RT-qPCR for markers relating to detection of circulating (CTCs) and disseminated tumour cells (DTCs), breast cancer clinicopathology, the 'cancer stem cell' phenotype, metabolism, hypoxia and epithelial-mesenchymal plasticity (EMP). Increased levels of SNAI1, ILK, NOTCH1, CK20, and PGR, and a decrease/loss of EPCAM in CTCs/DTCs were observed relative to the primary xenograft across both models. Decreased CD24 a..View full abstract
Awarded by National Health and Medical Research Council (Australia)
Awarded by National Breast Cancer Foundation, Australia (EMPathy National Collaborative Research Program)
Awarded by National Breast Cancer Foundation
This research was supported by the National Health and Medical Research Council (Australia, #1027527), the National Breast Cancer Foundation, Australia (EMPathy National Collaborative Research Program, CG-10-04) and St. Vincent's Hospital Research Endowment Fund-S.C. Dickensen Bequest. We gratefully acknowledge the generous support of the Vermont Cancer Research Fundraising Group, the Phyllis Connor Memorial Trust and the Angior Family Foundation for critical equipment. AT was supported by an Australian Postgraduate Award, AL was supported by an International Research Scholarship from the University of Melbourne and PhD top-up scholarships from the CRC for Cancer Therapeutics (CTx, CTx<SUP>2</SUP>), and E.W. Thompson was supported in part by the National Breast Cancer Foundation (CG-10-04; EMPathy). The Translational Research Institute receives support from the Australian Government.