A1 Refereed original research article in a scientific journal
CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer
Authors: Petruk Nataliia, Tuominen Sanni, Åkerfelt Malin, Mattsson Jesse, Sandholm Jouko, Nees Matthias, Yegutkin Gennady G., Jukkola Arja, Tuomela Johanna, Selander Katri S.
Publisher: NATURE RESEARCH
Publication year: 2021
Journal: Scientific Reports
Journal name in source: SCIENTIFIC REPORTS
Journal acronym: SCI REP-UK
Article number: ARTN 6035
Volume: 11
Issue: 1
Number of pages: 13
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-021-85379-z
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/53701319
CD73 is a cell surface ecto-5 ' -nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5 '-(alpha, beta -methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial-mesenchymal transition.
Downloadable publication This is an electronic reprint of the original article. |  |
