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Progesterone and its metabolite allopregnanolone promote invasion of human glioblastoma cells through metalloproteinase‑9 and cSrc kinase

  • Authors:
    • Claudia Bello-Alvarez
    • Carmen J. Zamora-Sánchez
    • Karla M. Peña-Gutiérrez
    • Ignacio Camacho-Arroyo

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  • Published online on: April 13, 2023     https://doi.org/10.3892/ol.2023.13809
  • Article Number: 223

  • Copyright: © Bello-Alvarez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioblastomas are the most aggressive and common primary brain tumors in adults. Glioblastoma cells have a great capacity to migrate and invade the brain parenchyma, often reaching the contralateral hemisphere. Progesterone (P4) and its metabolite, allopregnanolone (3α‑THP), promote the migration and invasion of human glioblastoma‑derived cells. P4 induces migration in glioblastoma cells by the activation of the proto‑oncogene tyrosine‑protein kinase Src (cSrc) and focal adhesion kinase (Fak). In breast cancer cells, cSrc and Fak promote invasion by increasing the expression and activation of extracellular matrix metalloproteinases (MMPs). However, the mechanism of action by which P4 and 3a-THP promote invasion in glioblastoma cells remains unclear. The effects of P4 and 3α‑THP on the protein expression levels of MMP‑2 and ‑9 and the participation of cSrc in progestin effects in U251 and U87 human glioblastoma‑derived cells were evaluated. It was determined by western blotting that the P4 increased the protein expression level of MMP‑9 in U251 and U87 cells, and 3α‑THP increased the protein expression level of MMP‑9 in U87 cells. None of these progestins modified MMP‑2 protein expression levels. The increase in MMP‑9 expression was reduced when the intracellular progesterone receptor and cSrc expression were blocked with small interfering RNAs. Cell invasion induced by P4 and 3α‑THP was also blocked by inhibiting cSrc activity with PP2 or by cSrc gene silencing. These results suggest that P4 and its metabolite 3α‑THP induce the invasion of glioblastoma cells by increasing MMP‑9 expression through the cSrc kinase family. The results of this study provide information of interest in the context of targeted therapies against molecular pathways involved in glioblastoma invasion.
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June-2023
Volume 25 Issue 6

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Spandidos Publications style
Bello-Alvarez C, Zamora-Sánchez CJ, Peña-Gutiérrez KM and Camacho-Arroyo I: Progesterone and its metabolite allopregnanolone promote invasion of human glioblastoma cells through metalloproteinase‑9 and cSrc kinase. Oncol Lett 25: 223, 2023.
APA
Bello-Alvarez, C., Zamora-Sánchez, C.J., Peña-Gutiérrez, K.M., & Camacho-Arroyo, I. (2023). Progesterone and its metabolite allopregnanolone promote invasion of human glioblastoma cells through metalloproteinase‑9 and cSrc kinase. Oncology Letters, 25, 223. https://doi.org/10.3892/ol.2023.13809
MLA
Bello-Alvarez, C., Zamora-Sánchez, C. J., Peña-Gutiérrez, K. M., Camacho-Arroyo, I."Progesterone and its metabolite allopregnanolone promote invasion of human glioblastoma cells through metalloproteinase‑9 and cSrc kinase". Oncology Letters 25.6 (2023): 223.
Chicago
Bello-Alvarez, C., Zamora-Sánchez, C. J., Peña-Gutiérrez, K. M., Camacho-Arroyo, I."Progesterone and its metabolite allopregnanolone promote invasion of human glioblastoma cells through metalloproteinase‑9 and cSrc kinase". Oncology Letters 25, no. 6 (2023): 223. https://doi.org/10.3892/ol.2023.13809