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Interleukin-3 production by basal-like breast cancer cells is associated with poor prognosis

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posted on 2024-02-01, 14:20 authored by Emma J. Thompson, Samantha Escarbe, Denis Tvorogov, Gelareh Farshid, Philip A. Gregory, Yeesim Khew-Goodall, Stephen Madden, Wendy V. Ingman, Geoffrey J. Lindeman, Elgene Lim, Angel F. Lopez, Claudine S. Bonder

Breast cancer represents a collection of pathologies with different molecular subtypes, histopathology, risk factors, clinical behavior, and responses to treatment. “Basal-like” breast cancers predominantly lack the receptors for estrogen and progesterone (ER/PR), lack amplification of human epidermal growth factor receptor 2 (HER2) but account for 10–15% of all breast cancers, are largely insensitive to targeted treatment and represent a disproportionate number of metastatic cases and deaths. Analysis of interleukin (IL)-3 and the IL-3 receptor subunits (IL-3RA + CSF2RB) reveals elevated expression in predominantly the basal-like group. Further analysis suggests that IL-3 itself, but not the IL-3 receptor subunits, associates with poor patient outcome. Histology on patient-derived xenografts supports the notion that breast cancer cells are a significant source of IL-3 that may promote disease progression. Taken together, these observations suggest that IL-3 may be a useful marker in solid tumors, particularly triple negative breast cancer, and warrants further investigation into its contribution to disease pathogenesis.

Funding

This project was funded by a Cancer Australia and the National Breast Cancer Foundation grant (CSB, AFL, GJL), a Health Services Charitable Gifts Board of the Royal Adelaide Hospital grant (CSB and AFL), the Australian Cancer Research Foundation (ACRF) Cancer Genomics Facility and the ACRF Discovery Accelerator Facility as well as a National Health and Medical Research Council Leadership Fellowship (GJL) and a University of South Australia Research Training Program and Australia Postgraduate Award post-graduate scholarship with a top-up from the Cell Therapy Manufacturing Co-operative Research Centre (EJT).

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