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

Miso Park, Jieun Kim, Nguyen T.T. Phuong, Jung Gyu Park, Jin Hee Park, Yong Chul Kim, Moon Chang Baek, Sung Chul Lim, Keon Wook Kang

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article number11587
JournalScientific Reports
Volume9
Issue number1
DOIs
StatePublished - 1 Dec 2019

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Tamoxifen
Breast Neoplasms
Neoplasm Metastasis
MCF-7 Cells
Extracellular Vesicles
Proteins
Epithelial-Mesenchymal Transition
Liver
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Estrogen Receptors
Therapeutics
Spleen
Messenger RNA

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Park, Miso ; Kim, Jieun ; Phuong, Nguyen T.T. ; Park, Jung Gyu ; Park, Jin Hee ; Kim, Yong Chul ; Baek, Moon Chang ; Lim, Sung Chul ; Kang, Keon Wook. / Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer : effects on small extracellular vesicles production. In: Scientific Reports. 2019 ; Vol. 9, No. 1.
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Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer : effects on small extracellular vesicles production. / Park, Miso; Kim, Jieun; Phuong, Nguyen T.T.; Park, Jung Gyu; Park, Jin Hee; Kim, Yong Chul; Baek, Moon Chang; Lim, Sung Chul; Kang, Keon Wook.

In: Scientific Reports, Vol. 9, No. 1, 11587, 01.12.2019.

Research output: Contribution to journalArticle

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T1 - Involvement of the P2X7 receptor in the migration and metastasis of tamoxifen-resistant breast cancer

T2 - effects on small extracellular vesicles production

AU - Park, Miso

AU - Kim, Jieun

AU - Phuong, Nguyen T.T.

AU - Park, Jung Gyu

AU - Park, Jin Hee

AU - Kim, Yong Chul

AU - Baek, Moon Chang

AU - Lim, Sung Chul

AU - Kang, Keon Wook

PY - 2019/12/1

Y1 - 2019/12/1

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AB - 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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