RT Journal Article
T1 Cannabinoids inhibit glioma cell invasion by down-regulating matrix metalloproteinase-2 expression
A1 Blázquez Ortiz, Cristina
A1 Salazar Roa, María
A1 Arkaitz Carracedo, Arkaitz
A1 Lorente Pérez, María Del Mar
A1 Egia, Ainara
A1 Gonzalez Feria, Luis
A1 Haro Ramos, Amador De
A1 Velasco Díez, Guillermo
A1 Guzmán Pastor, Manuel
AB Cannabinoids, the active components of Cannabis sativa L. and their derivatives, inhibit tumor growth in laboratory animals by inducing apoptosis of tumor cells and impairing tumor angiogenesis. It has also been reported that these compounds inhibit tumor cell spreading, but the molecular targets of this cannabinoid action remain elusive. Here, we evaluated the effect of cannabinoids on matrix metallopro- teinase (MMP) expression and its effect on tumor cell invasion. Local administration of #9-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down- regulated MMP-2 expression in gliomas generated in mice, as determined by Western blot, immunofluorescence, and real-time quantitative PCR analyses. This cannabinoid- induced inhibition of MMP-2 expression in gliomas (a) was MMP-2–selective, as levels of other MMP family members were unaffected; (b) was mimicked by JWH-133, a CB2 cannabinoid receptor–selective agonist that is devoid of psychoactive side effects; (c) was abrogated by fumonisin B1, a selective inhibitor of ceramide biosynthesis; and (d) was also evident in two patients with recurrent glioblastoma multiforme. THC inhibited MMP-2 expression and cell invasion in cultured glioma cells. Manipulation of MMP-2 expression by RNA interference and cDNA overexpression experiments proved that down-regulation of this MMP plays a critical role in THC- mediated inhibition of cell invasion. Cannabinoid-induced inhibition of MMP-2 expression and cell invasion was prevented by blocking ceramide biosynthesis and by knock- ing-down the expression of the stress protein p8. As MMP-2 up-regulation is associated with high progression and poor prognosis of gliomas and many other tumors, MMP-2 down- regulation constitutes a new hallmark of cannabinoid anti- tumoral activity.
PB American Association for Cancer Research
SN 0008-5472
YR 2008
FD 2008
LK https://hdl.handle.net/20.500.14352/97836
UL https://hdl.handle.net/20.500.14352/97836
LA eng
NO Cristina Blázquez, María Salazar, Arkaitz Carracedo, Mar Lorente, Ainara Egia, Luis González-Feria, Amador Haro, Guillermo Velasco, Manuel Guzmán; Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression. Cancer Res 15 March 2008; 68 (6): 1945–1952. https://doi.org/10.1158/0008-5472.CAN-07-5176
NO Ministerio de Educación y Ciencia (España)
NO Universidad Complutense de Madrid
NO Eusko Jaurlaritza
DS Docta Complutense
RD 22 abr 2025