Email updates

Keep up to date with the latest news and content from Molecular Cancer and BioMed Central.

Open Access Research

Characteristics of CD44 alternative splice pattern in the course of human colorectal adenocarcinoma progression

Balázs Bánky12*, Lívia Rásó-Barnett13, Tamás Barbai1, József Tímár14, Péter Becságh1 and Erzsébet Rásó14

Author Affiliations

1 2nd Institute of Pathology, Semmelweis University, Üllői út 93., 1091, Budapest, Hungary

2 St Borbála Hospital, Department of Surgery and Vascular Surgery, Dózsa Gy. út 77., 2800, Tatabánya, Hungary

3 Guy’s and St. Thomas’ Hospital, Westminster Bridge Road, London, SE1 7EH, United Kingdom

4 Tumour Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary

For all author emails, please log on.

Molecular Cancer 2012, 11:83  doi:10.1186/1476-4598-11-83

Published: 14 November 2012

Abstract

Background

CD44 is considered as ‘a’ metastasis associated gene, despite the fact that it is an umbrella term for a group of molecules produced from a single gene by alternative splicing. However, little consideration is given to the above in the literature of colorectal carcinomas as well as other tumour types, leading to confusion and contradictory results about its possible role in tumour progression.

Methods

We compared the CD44 alternative splice pattern (ASP) of three genetically different human colorectal cancer cell lines (HT25, HT29, HCT116) using a series of PCR reactions and next- generation sequencing method, as well as identified a colorectal adenocarcinoma specific CD44 ASP. This ASP was further investigated in terms of its qualitative and quantitative stability in our experimental iso- and xenograft mouse models for colorectal cancer progression. A complex preclinical experimental set-up was established to separately test the different steps of tumour progression and the role of tumour microenvironment, respectively, focusing on the role of ‘CD44’ in this process.

Results

We managed to present a colorectal cancer-specific CD44 ASP, which remained unchanged from cell lines throughout primary tumour formation and metastatic progression. Furthermore, we report a unique roster of all expressed CD44 variant isoforms characteristic to colorectal cancer. Finally, on quantitative assessment of the variable exons v3 and v6, higher co-expression levels were found to be characteristic to metastatically potent tumour cells.

Conclusion

Particular CD44 variant isoforms seem to act as “metastasis genes” via tumour microenvironment-driven shifts in v3 and v6 expressions. However, this function may just affect a minority of tumour subclones. This fact and the huge potential number of different CD44 splice variants that can contain v3 and v6 domains can explain incoherence of clinical studies regarding functional asessment of CD44 variants, as well as diminish the chances of using CD44 variants for predictive purpose.

Keywords:
CD44; v3; v6; Alternative; Splicing; Metastasis; Colorectal; Cancer; Microenvironment