A partir d'une base de données portant sur 1 172 échantillons de tumeurs mammaires prélevés sur 26 modèles murins différents, cette étude décrit diverses caractéristiques moléculaires de ces tumeurs et analyse leurs relations avec celles des cancers du sein dans l'espèce humaine

A genomic analysis of mouse models of breast cancer reveals molecular features of mouse models and relationships to human breast cancer

Hollern, Daniel ; Andrechek, Eran

INTRODUCTION:Genomic variability limits the efficacy of breast cancer therapy. To simplify the study of the molecular complexity of breast cancer, researchers have used mouse mammary tumor models. However, the degree to which mouse models model human breast cancer and are reflective of the human heterogeneity has yet to be demonstrated with gene expression studies on a large scale. METHODS:To this end, we have built a database consisting of 1,172 mouse mammary tumor samples from 26 different [...]

Menée à l'aide de modèles murins, cette étude met en évidence des mécanismes par lesquels l'expression du gène SOX2 dans les cellules souches cancéreuses favorise le développement et la progression d'un carcinome spinocellulaire

SOX2 controls tumour initiation and cancer stem-cell functions in squamous-cell carcinoma

Boumahdi, Soufiane ; Driessens, Gregory ; Lapouge, Gaelle ; Rorive, Sandrine ; Nassar, Dany ; Le Mercier, Marie ; Delatte, Benjamin ; Caauwe, Amelie ; Lenglez, Sandrine ; Nkusi, Erwin ; Brohee, Sylvain ; Salmon, Isabelle ; Dubois, Christine ; Marmol, Veronique del ; Fuks, Francois ; Beck, Benjamin ; Blanpain, Cedric

Cancer stem cells (CSCs) have been reported in various cancers, including in skin squamous-cell carcinoma (SCC). The molecular mechanisms regulating tumour initiation and stemness are still poorly characterized. Here we find that Sox2, a transcription factor expressed in various types of embryonic and adult stem cells, was the most upregulated transcription factor in the CSCs of squamous skin tumours in mice. SOX2 is absent in normal epidermis but begins to be expressed in the vast majority of [...]

Menée à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels le micro-ARN miR-128 exerce une fonction de suppresseur de tumeurs dans le cancer de la prostate

MicroRNA-128 suppresses prostate cancer by inhibiting BMI-1 to inhibit tumor-initiating cells

Jin, Min ; Zhang, Tao ; Liu, Can ; Badeaux, Mark A ; Liu, Bigang ; Liu, Ruifang ; Jeter, Collene ; Chen, Xin ; Vlassov, Alexander V. ; Tang, Dean G

MicroRNA-128 (miR-128) is reduced in prostate cancer (PCa) relative to normal/benign prostate tissues but causal roles are obscure. Here we show that exogenously introduced miR-128 suppresses tumor regeneration in multiple PCa xenograft models. Cancer stem-like cell (CSC) associated properties were blocked, including holoclone and sphere formation as well as clonogenic survival. Using a miR-128 sensor to distinguish cells on the basis of miR-128 expression, we found that miR-128-lo cells [...]

Menée à l'aide de xénogreffes, cette étude met en évidence des mécanismes par lesquels, en régulant la signalisation WNT, les gènes TMED3 et SOX12 exercent une fonction de suppresseur de métastases dans le cancer du côlon

A novel genome-wide in vivo screen for metastatic suppressors in human colon cancer identifies the positive WNT-TCF pathway modulators TMED3 and SOX12

Duquet, Arnaud ; Melotti, Alice ; Mishra, Sonakshi ; Malerba, Monica ; Seth, Chandan ; Conod, Arwen ; Ruiz i Altaba, Ariel

The progression of tumors to the metastatic state involves the loss of metastatic suppressor functions. Finding these, however, is difficult as in vitro assays do not fully predict metastatic behavior, and the majority of studies have used cloned cell lines, which do not reflect primary tumor heterogeneity. Here, we have designed a novel genome-wide screen to identify metastatic suppressors using primary human tumor cells in mice, which allows saturation screens. Using this unbiased approach, [...]

Menée à l'aide de xénogreffes sur un modèle murin, cette étude met en évidence des mécanismes par lesquels l'isoforme gamma de la cytokine CXCL12 favorise le processus métastatique d'un cancer du sein

CXCL12-

Ray, P. ; Stacer, A. C. ; Fenner, J. ; Cavnar, S. P. ; Meguiar, K. ; Brown, M. ; Luker, K. E. ; Luker, G. D.

Compelling evidence shows that chemokine C-X-C motif chemokine ligand 12 (CXCL12) drives metastasis in multiple malignancies. Similar to other key cytokines in cancer, CXCL12 exists as several isoforms with distinct biophysical properties that may alter signaling and functional outputs. However, effects of CXCL12 isoforms in cancer remain unknown. CXCL12-[alpha], -[beta] and -[gamma] showed cell-type-specific differences in activating signaling through G protein-dependent pathways in cell-based [...]

Cet article passe en revue les travaux récents sur l'usage de systèmes tridimensionnels in vitro pour l'étude du micro-environnement tumoral

Three-dimensional cancer models mimic cell-matrix interactions in the tumour microenvironment

Herrmann, David ; Conway, James R.W. ; Vennin, Claire ; Magenau, Astrid ; Hughes, William G. ; Morton, Jennifer P. ; Timpson, Paul

Basic in vitro systems can be used to model and assess complex diseases, such as cancer. Recent advances in this field include the incorporation of multiple cell types and extracellular matrix proteins into 3D models to recapitulate the structure, organization and functionality of live tissue in situ. Cells within such a 3D environment behave very differently from cells on 2D substrates, as cell-matrix interactions trigger signalling pathways and cellular responses in 3D, which may not be [...]