Loss of Endocan tumorigenic properties after alternative splicing of exon 2.

Florence Depontieu, Bogdan-Dragos Grigoriu, Arnaud Scherpereel, Estelle Adam, Maryse Delehedde, Philippe Gosset, Philippe Lassalle

Index: BMC Cancer 8 , 14, (2008)

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Abstract

Endocan was originally described as a dermatan sulfate proteoglycan found freely circulating in the blood. Endocan expression confers tumorigenic properties to epithelial cell lines or accelerate the growth of already tumorigenic cells. This molecule is the product of a single gene composed of 3 exons. Previous data showed that endocan mRNA is subject to alternative splicing with possible generation of two protein products. In the present study we identified, and functionally characterized, the alternative spliced product of the endocan gene: the exon 2-deleted endocan, called endocanDelta2.Stable, endocanDelta2-overexpressing cell lines were generated to investigate the biological activities of this new alternatively spliced product of endocan gene. Tumorigenesis was studied by inoculating endocan and endocanDelta2 expressing cell lines subcutaneously in SCID mice. Biochemical properties of endocan and endocanDelta2 were studied after production of recombinant proteins in various cell lines of human and murine origin.Our results showed that the exon 2 deletion impairs synthesis of the glycan chain, known to be involved in the pro-tumoral effect of endocan. EndocanDelta2 did not promote tumor formation by 293 cells implanted in the skin of severe combined immunodeficient (SCID) mice.Our results emphasize the key role of the polypeptide sequence encoded by the exon 2 of endocan gene in tumorigenesis, and suggest that this sequence could be a target for future therapies against cancer.