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Cristina Sánchez
 
 

                      

 

                      

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Cristina Sánchez, PhD

Telephone: +34 913944668

Fax:         +34 913944672

E-mail: cristina.sanchezquim.ucm.es

                                                         

 
Research

Breast cancer is one of the leading causes of death amongst Western women. Although the mortality rates associated with this disease are decreasing, the need for new therapies is obvious because most recurrences are lethal and certain cases remain reluctant to conventional treatments. It has been demonstrated that cannabinoids induce antiproliferative, antiangiogenic and antimetastatic effects in several animal models of cancer, which make them potential antitumoral agents.

Antitumoral effect of cannabinoids on breast cancer.

Our work has demonstrated that cannabinoids reduce human breast cancer cell proliferation and induce cancer cell death by apoptosis. The study of the molecular mechanisms underlying this effect has allowed us to propose a model that includes the blockade of the cell cycle in the transition from G2 to mitosis and the inhibition of the JunD transcription factor, a member of the AP-1 family.

 

Antitumoral effect of cannabinoids in vivo.

 

Although the antitumoral action of cannabinoids has been demonstrated in different models of cancer, most of them are based on xenografts, which are useful but limited tools. These models rely on the propagation of tumor cells in immunodeficient mice at ectopic or orthotopic sites and lack crucial features of patients’ tumors such as the actual tumor architecture and the interactions with the tumor microenvironment, including normal non-cancerous surrounding tissue, vasculature and immune cells. We are currently using a genetically engineered animal model of breast cancer to analyze the effect of cannabinoids on tumor progression and generation.

Antitumoral effect mediated by non-psychotropic cannabinoid receptors.

It is known that cannabinoids exert a number of psychotropic actions, which make difficult to use them in the clinic. However, most of these effects are mediated by CB1 receptors exclusively. Thus, the selective activation of other cannabinoid receptors different than CB1 would be an alternative strategy to evoke their therapeutic effects. Our data show that CB2 receptor mediates the antitumoral effect of cannabinoids on breast cancer. Moreover, we have observed a correlation between CB2 expression and tumor malignancy. We are currently generating mice with two genetic manipulations (transgenic for neu oncogen plus CB2 knock-out) to understand the involvement of this receptor in oncogenesis and tumor progression.  

Antitumoral effect mediated by other cannabinoid receptors.

There is evidence pointing to the existence of cannabinoid receptors other than CB1 and CB2. Preliminary data obtained in our group point to the participation of some of them in the effect of cannabinoids on cancer cell proliferation, not only in breast cancer but in many type of tumors. We are currently analyzing this participation by both in vitro and in vivo approaches.

 

Selected publications

I. Galve-Roperh, C. Sánchez, M.L. Cortés, T. Gómez del Pulgar, M. Izquierdo, M. Guzmán

Antitumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation

Nat. Med. 6, 313-319 (2000)

 

C. Sánchez, M.L. de Ceballos, T. Gómez del Pulgar, D. Rueda, C. Corbacho, G. Velasco, I. Galve-Roperh, J.W. Huffman, S. Ramón y Cajal, M. Guzmán

Inhibition of glioma growth in vivo by selective activation of the CB2 cannabinoid receptor

Cancer Res. 61, 5784-5789 (2001)

 

M.M. Caffarel, D. Sarrió, J. Palacios, M. Guzmán, C. Sánchez

D9-Tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation

Cancer Res. 66, 6615-6621 (2006)

 

M.M. Caffarel, G. Moreno-Bueno, C. Cerutti, J. Palacios, M. Guzmán, F. Mechta-Grigoriou, C. Sánchez

JunD is involved in D9-tetrahydrocannabinol antiproliferative effect on human breast cancer cells

Oncogene 27, 5033-5044 (2008)

 

M.M. Caffarel, C. Andradas, E. Mira, C. Cerutti, J.M. Flores, G. Moreno-Bueno, I. García-Real, J. Palacios, S. Mañes, M. Guzmán, C.

Sánchez

Cannabinoids reduce ErbB2-driven breast cancer progression through Akt inhibition

Mol. Cancer 9, 196 (2010)     

 

C. Andradas, M.M. Caffarel, E. Pérez-Gómez, M. Salazar, M. Lorente, G. Velasco, M. Guzmán, C. Sánchez

The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK

Oncogene (aceptado, 2010)

 

 

Methodology

In order to carry out our projects, we use a multidisciplinary methodology which includes biochemical and pharmacological approaches, molecular biology tools, and the use and generation of genetically modified animal models. In particular, we analyze gen and protein expression by semiquantitative and quantitative PCR and DNA arrays (genes) and Western blotting and immunofluorescence (proteins), we modulate the expression of proteins with plasmids, adeno- and retroviruses (overexpression) and small interference RNA (silencing), we use different in vitro (cell culture) and in vivo (ecto- and orthotopic xenografts in immune-deficient mice, transgenic mice) models of cancer, etc.

 

Collaborations

Our group actively collaborates with other labs. Here there is a list of some of them: 

Andrew Irving, Universidad de Dundee, Dundee, Reino Unido:

http://www.dundee.ac.uk/cmdn/staff/andrew_irving

Santos Mañes, Centro Nacional de Biotecnología, Madrid, España:

http://www.cnb.uam.es/content/research/immunoncology/lipidrafts/index.php?l=0

Fatima Mechta-Grigoriou, Instituto Marie Curie, Paris, Francia:

http://www.curie.fr/recherche/themes/equipe_histoire.cfm/id_equipe/318/lang/_gb.htm 

Gema Moreno, Instituto de Investigaciones Biomédicas “Alberto Sols”, Madrid, España:

http://www.iib.uam.es/script/personas.es.cgi?codigo=165

Maria Waldhoer, Universidad de Graz, Graz, Austria:

http://www.medunigraz.at/pharma/