<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Fico, Flavia</dc:creator>
  <dc:creator>Santamaria‐Martínez, Albert</dc:creator>
  <dc:date>2020-10-16</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Breast cancer metastasis is a complex process that depends not only on intrinsic  characteristics of metastatic stem cells, but also on the particular microenvironment  that supports their growth and modulates the plasticity of the system. In search for  microenvironmental factors supporting cancer stem cell (CSC) growth and tumour  progression to metastasis, we here investigated the role of the matricellular protein  transforming growth factor beta induced (TGFBI) in breast cancer. We crossed the  MMTV‐PyMT model of mammary gland tumorigenesis with a TgfbiΔ/Δ mouse and  studied the CSC content of the tumours. We performed RNAseq on wt and ko  tumours, and analysed the tumour vasculature and the immune compartment by IHC  and FACS. The source of TGFBI expression was determined by qPCR and by bone  marrow transplantation experiments. Finally, we performed in silico analyses using the  METABRIC cohort to assess the potential prognostic value of TGFBI. We observed  that deletion of Tgfbi led to a dramatic decrease in CSC content and lung metastasis.  Our results show that lack of TGFBI resulted in tumour vessel normalisation, with  improved vessel perfusion and decreased hypoxia, a major factor controlling CSCs  and metastasis. Furthermore, human data mining in a cohort of breast cancer patients  showed that higher expression of TGFBI correlates with poor prognosis and is  associated with the more aggressive subtypes of breast cancer. Overall, these data  reveal a novel biological mechanism controlling metastasis that could potentially be  exploited to improve the efficacy and delivery of chemotherapeutic agents in breast  cancer.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://folia.unifr.ch/global/documents/309051</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/309051/files/san_tmt.pdf</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/309051/files/san_tmt_sm.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1002/1878-0261.12828</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>License undefined</dc:rights>
  <dc:source>Molecular Oncology. - 2020, vol. 14, no. 12, p. 3198–3210</dc:source>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns1="xml" ns1:lang="en">TGFBI modulates tumour hypoxia and promotes breast cancer metastasis</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>