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Matrix Biol. 2012 Jun;31(5):285-9. doi: 10.1016/j.matbio.2012.03.003. Epub 2012 Apr 16.

Tumor suppression by collagen XV is independent of the restin domain.

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1
Human Molecular Genetics Program, Children's Memorial Research Center, and Department of Pediatrics, Northwestern University Feinberg School of Medicine, 2300 Children's Plaza #211, Chicago, IL 60614, USA.

Abstract

Non-fibrillar collagen XV is a chondroitin sulfate modified glycoprotein that is associated with the basement membrane zone in many tissues. Its precise functions remain to be fully elucidated though it clearly plays a critical role in the structural integrity of the extracellular matrix. Loss of collagen XV from the basement membrane zone precedes invasion of a number of tumor types and we previously showed that collagen XV functions as a dose-dependent suppressor of tumorigenicity in cervical carcinoma cells. The carboxyl terminus of another non-fibrillar collagen (XVIII) is cleaved to produce endostatin, which has anti-angiogenic effects and thus may act as a tumor suppressor in vivo. Since collagen XV has structural similarity with collagen XVIII, its C-terminal restin domain could confer tumor suppressive functions on the molecule, though our previous data did not support this. We now show that expression of collagen XV enhances the adhesion of cervical carcinoma cells to collagen I in vitro as does the N-terminus and collagenous regions of collagen XV, but not the restin domain. Destruction of a cysteine residue in the collagenous region that is critical for intermolecular interactions of collagen XV abolished the enhanced adhesion to collagen I. Finally, we demonstrate that unlike full length collagen XV, expression of the restin domain alone does not suppress tumorigenicity of cervical carcinoma cells in vivo; hence, this process is dependent on functions and interactions of other parts of the protein.

PMID:
22531369
PMCID:
PMC3373166
DOI:
10.1016/j.matbio.2012.03.003
[Indexed for MEDLINE]
Free PMC Article
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