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Loss of Endocan tumorigenic properties after alternative splicing of exon 2

Domenii publicaţii > Ştiinţe medicale + Tipuri publicaţii > Articol în revistã ştiinţificã

Autori: Depontieu F, Grigoriu BD, Scherpereel A, Adam E., Delehedde M., Gosset Ph., Lassalle Ph.

Editorial: BMC Cancer, 8, p.14 (p1-8), 2008.


Background: 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 endocanΔ2.
Methods: Stable, endocanΔ2-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 endocanΔ2 expressing cell lines subcutaneously in SCID mice. Biochemical
properties of endocan and endocanΔ2 were studied after production of recombinant proteins in
various cell lines of human and murine origin.
Results: 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. EndocanΔ2 did not promote tumor formation
by 293 cells implanted in the skin of severe combined immunodeficient (SCID) mice.
Conclusion: 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.

Cuvinte cheie: celula endoteliala, tumorigeneza // endotelial cell, tumorigenesis