Deletion of Cd151 reduces mammary tumorigenesis in the MMTV/PyMT mouse model

BMC Cancer

Séverine Roselli²  Richard GS Kahl²  Ben T Copeland²  Matthew J Naylor¹  Judith Weidenhofer²  William J Muller³  Leonie K Ashman² 

[1] School of Medical Sciences, University of Sydney, Sydney, NSW, Australia

[2] Hunter Medical Research Institute, Cancer Research Program, Newcastle, NSW, Australia

[3] Goodman Cancer Centre, McGill University, Montreal, Canada

关键词: Metastasis;    Cancer;    Breast;    CD151;    Tetraspanin;   

Others  :  1125344
DOI  :  10.1186/1471-2407-14-509

 received in 2014-02-19, accepted in 2014-07-04,  发布年份 2014

【 摘 要 】

Background

Tetraspanins are transmembrane proteins that serve as scaffolds for multiprotein complexes containing, for example, integrins, growth factor receptors and matrix metalloproteases, and modify their functions in cell adhesion, migration and transmembrane signaling. CD151 is part of the tetraspanin family and it forms tight complexes with β1 and β4 integrins, both of which have been shown to be required for tumorigenesis and/or metastasis in transgenic mouse models of breast cancer. High levels of the tetraspanin CD151 have been linked to poor patient outcome in several human cancers including breast cancer. In addition, CD151 has been implicated as a promoter of tumor angiogenesis and metastasis in various model systems.

Methods

Here we investigated the effect of Cd151 deletion on mammary tumorigenesis by crossing Cd151-deficient mice with a spontaneously metastasising transgenic model of breast cancer induced by the polyoma middle T antigen (PyMT) driven by the murine mammary tumor virus promoter (MMTV).

Results

Cd151 deletion did not affect the normal development and differentiation of the mammary gland. While there was a trend towards delayed tumor onset in Cd151^−/− PyMT mice compared to Cd151^+/+ PyMT littermate controls, this result was only approaching significance (Log-rank test P-value =0.0536). Interestingly, Cd151 deletion resulted in significantly reduced numbers and size of primary tumors but did not appear to affect the number or size of metastases in the MMTV/PyMT mice. Intriguingly, no differences in the expression of markers of cell proliferation, apoptosis and blood vessel density was observed in the primary tumors.

Conclusion

The findings from this study provide additional evidence that CD151 acts to enhance tumor formation initiated by a range of oncogenes and strongly support its relevance as a potential therapeutic target to delay breast cancer progression.

【 授权许可】

   
2014 Roselli et al.; licensee BioMed Central Ltd.

【 图 表 】

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