TGFBI modulates tumour hypoxia and promotes breast cancer metastasis

• DOI: 10.1002/1878-0261.12828
• Publication Date: 2020-10-20T17:08:32Z
• Authors: Flavia Fico; Albert Santamaria...
• Keywords: TGFBI

Breast cancer metastasis is a complex process that depends not only on intrinsic characteristics of metastatic stem cells, but also the particular microenvironment supports their growth and modulates plasticity system. In search for microenvironmental factors supporting cell (CSC) tumour progression to metastasis, we here investigated role matricellular protein transforming factor beta induced (TGFBI) in breast cancer. We crossed MMTV-PyMT model mammary gland tumorigenesis with TgfbiΔ/Δ mouse studied CSC content tumours. performed RNAseq wt ko tumours, analysed vasculature immune compartment by IHC FACS. The source TGFBI expression was determined qPCR bone marrow transplantation experiments. Finally, silico analyses using METABRIC cohort assess potential prognostic value TGFBI. observed deletion Tgfbi led dramatic decrease lung metastasis. Our results show lack resulted vessel normalisation, improved perfusion decreased hypoxia, major controlling CSCs Furthermore, human data mining patients showed higher correlates poor prognosis associated more aggressive subtypes Overall, these reveal novel biological mechanism could potentially be exploited improve efficacy delivery chemotherapeutic agents