2. Academic Validation
  3. Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer: effects on small extracellular vesicles production

Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer: effects on small extracellular vesicles production

  • Sci Rep. 2019 Aug 12;9(1):11587. doi: 10.1038/s41598-019-47734-z.
Miso Park 1,  Jieun Kim 1,  Nguyen T T Phuong 1,  Jung Gyu Park 1,  Jin-Hee Park 2,  Yong-Chul Kim 2,  Moon Chang Baek 3,  Sung Chul Lim 4,  Keon Wook Kang 5
Affiliations

Affiliations

  • 1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
  • 2 School of Life Sciences, Gwangju Institute of Science & Technology, Gwangju, 61005, Republic of Korea.
  • 3 Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
  • 4 Department of Pathology, College of Medicine, Chosun University, Gwangju, 61452, Republic of Korea.
  • 5 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea. [email protected].
PMID: 31406126 DOI: 10.1038/s41598-019-47734-z
Abstract

Tamoxifen (TAM) is the standard anti-hormonal therapy for estrogen receptor-positive breast Cancer. However, long-term TAM therapy can make acquisition of TAM resistance and there are still no solutions to treat TAM-resistant breast Cancer. In this study, we found that protein and mRNA expression of the P2X purinoreceptor 7 (P2X7) was higher in tamoxifen resistant MCF-7 (TAMR-MCF-7) cells than in control MCF-7 cells. P2X7 inhibition potently inhibited the migration of TAMR-MCF-7 cells and the liver metastasis burden of TAMR-MCF-7 cells in the spleen-liver metastasis experiment. However, the P2X7 antagonist did not affect protein expression of matrix metalloproteinase (MMP)-2, MMP-9, and epithelial-mesenchymal transition markers. Here our data indicate a link between small extracellular vesicles (sEV) and P2X7, and suggest a new mechanism of metastasis in TAM-resistant breast Cancer cells through P2X7 receptors. The migration of TAMR-MCF-7 cells was increased in a concentration-dependent manner by purified sEV treatment. The number of secreted sEVs and the protein levels of CD63 in TAMR-MCF-7 cells were decreased by the P2X7 antagonist, showing that P2X7 influences the production of sEV. Our results suggest that inhibiting the P2X7 could be considered for metastasis prevention in TAM-resistant Cancer patients.

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