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Mol. Cells 2009; 27(5): 503-513

Published online May 15, 2009

https://doi.org/10.1007/s10059-009-0069-0

© The Korean Society for Molecular and Cellular Biology

Basement Membrane Proteoglycans: Modulators Par Excellence of Cancer Growth and Angiogenesis

Renato V. Iozzo, Jason J. Zoeller, and Alexander Nystroem

Received: April 22, 2009; Accepted: April 25, 2009

Abstract

Proteoglycans located in basement membranes, the nanos-tructures underling epithelial and endothelial lay-ers, are unique in several respects. They are usually large, elon-gated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more “active configuration” to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical for the evolution of the tumor microenvironment. This review will focus on the func-tional roles of the major heparan sulfate proteoglycans from basement membrane zones: perlecan, agrin and collagen XVIII, and on their roles in modulating cancer growth and angiogenesis.

Keywords agrin, angiogenesis, cancer, collagen XVIII, endorepellin, endostatin, heparan sulfate proteoglycans, perlecan

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Mol. Cells 2009; 27(5): 503-513

Published online May 31, 2009 https://doi.org/10.1007/s10059-009-0069-0

Copyright © The Korean Society for Molecular and Cellular Biology.

Basement Membrane Proteoglycans: Modulators Par Excellence of Cancer Growth and Angiogenesis

Renato V. Iozzo, Jason J. Zoeller, and Alexander Nystroem

Received: April 22, 2009; Accepted: April 25, 2009

Abstract

Proteoglycans located in basement membranes, the nanos-tructures underling epithelial and endothelial lay-ers, are unique in several respects. They are usually large, elon-gated molecules with a collage of domains that share structural and functional homology with numerous extracellular matrix proteins, growth factors and surface receptors. They mainly carry heparan sulfate side chains and these contribute not only to storing and preserving the biological activity of various heparan sulfate-binding cytokines and growth factors, but also in presenting them in a more “active configuration” to their cognate receptors. Abnormal expression or deregulated function of these proteoglycans affect cancer and angiogenesis, and are critical for the evolution of the tumor microenvironment. This review will focus on the func-tional roles of the major heparan sulfate proteoglycans from basement membrane zones: perlecan, agrin and collagen XVIII, and on their roles in modulating cancer growth and angiogenesis.

Keywords: agrin, angiogenesis, cancer, collagen XVIII, endorepellin, endostatin, heparan sulfate proteoglycans, perlecan

Mol. Cells
Sep 30, 2023 Vol.46 No.9, pp. 527~572
COVER PICTURE
Chronic obstructive pulmonary disease (COPD) is marked by airspace enlargement (emphysema) and small airway fibrosis, leading to airflow obstruction and eventual respiratory failure. Shown is a microphotograph of hematoxylin and eosin (H&E)-stained histological sections of the enlarged alveoli as an indicator of emphysema. Piao et al. (pp. 558-572) demonstrate that recombinant human hyaluronan and proteoglycan link protein 1 (rhHAPLN1) significantly reduces the extended airspaces of the emphysematous alveoli by increasing the levels of TGF-β receptor I and SIRT1/6, as a previously unrecognized mechanism in human alveolar epithelial cells, and consequently mitigates COPD.

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