Dataset Information

Demonstration of a melanoma-specific CD44 alternative splicing pattern that remains qualitatively stable, but shows quantitative changes during tumour progression.

ABSTRACT: The role of CD44 in the progression of human melanoma has mostly been characterised by qualitative changes in expression of its individual variable exons. These exons however, may be expressed to form a number of molecules, the alternative splice variants of CD44, which may be structurally and functionally different. Using real-time PCR measurements with variable exon specific primers we have determined that all are expressed in human melanoma. To permit comparison between different tumours we identified a stable CD44 variable exon (CD44v) expression pattern, or CD44 'fingerprint'. This was found to remain unchanged in melanoma cell lines cultured in different matrix environments. To evaluate evolution of this fingerprint during tumour progression we established a scid mouse model, in which the pure expression pattern of metastatic primary tumours, circulating cells and metastases, non-metastatic primary tumours and lung colonies could be studied. Our analyses demonstrated, that although the melanoma CD44 fingerprint is qualitatively stable, quantitative changes are observed suggesting a possible role in tumour progression.

SUBMITTER: Raso-Barnett L

PROVIDER: S-EPMC3544768 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Demonstration of a melanoma-specific CD44 alternative splicing pattern that remains qualitatively stable, but shows quantitative changes during tumour progression.

Raso-Barnett Livia L Banky Balazs B Barbai Tamas T Becsagh Peter P Timar Jozsef J Raso Erzsebet E

PloS one 20130114 1

The role of CD44 in the progression of human melanoma has mostly been characterised by qualitative changes in expression of its individual variable exons. These exons however, may be expressed to form a number of molecules, the alternative splice variants of CD44, which may be structurally and functionally different. Using real-time PCR measurements with variable exon specific primers we have determined that all are expressed in human melanoma. To permit comparison between different tumours we i ...[more]

PMID: 23342032

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Project description: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.

Dataset Information

Demonstration of a melanoma-specific CD44 alternative splicing pattern that remains qualitatively stable, but shows quantitative changes during tumour progression.

Publications

Demonstration of a melanoma-specific CD44 alternative splicing pattern that remains qualitatively stable, but shows quantitative changes during tumour progression.

Similar Datasets

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