Matrix protease production, epithelial-to-mesenchymal transition marker expression and invasion of glioblastoma cells in response to osmotic or hydrostatic pressure.
Sci Rep
; 10(1): 2634, 2020 02 14.
Article
en En
| MEDLINE
| ID: mdl-32060379
ABSTRACT
Both hydrostatic and osmotic pressures are altered in the tumour microenvironment. Glioblastoma (GBM) is a brain tumour with high invasiveness and poor prognosis. We hypothesized that physical and osmotic forces regulate glioblastoma (GBM) invasiveness. The osmotic pressure of GBM cell culture medium was adjusted using sodium chloride or water. Alternatively, cells were subjected to increased hydrostatic force. The proteolytic profile and epithelial-mesenchymal transition (EMT) were investigated using zymography and real-time qPCR. The EMT markers assessed were Snail-1, Snail-2, N-cadherin, Twist and vimentin. Invasion was investigated in vitro using extracellular matrix-coated Transwell inserts. In response to osmotic and mechanical pressure, GBM cell lines U87 and U251 and patient-derived neural oncospheres upregulated the expression of urokinase-type plasminogen activator (uPA) and/or matrix metalloproteinases (MMPs) as well as some of the EMT markers tested. The adherent cell lines invaded more when placed in media of increased osmolality. Therefore, GBM respond to osmotic or mechanical pressure by increasing matrix degrading enzyme production, and adopting a phenotype reminiscent of EMT. Better understanding the molecular and cellular mechanisms by which increased pressure promotes GBM invasiveness may help to develop innovative therapeutic approaches.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
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Glioblastoma
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Metaloproteinasas de la Matriz
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Transición Epitelial-Mesenquimal
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Invasividad Neoplásica
Límite:
Humans
Idioma:
En
Revista:
Sci Rep
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia