Matrix hyaluronan alters epidermal growth factor receptor-dependent cell morphology.
Journal: 2010/September - Cell Adhesion and Migration
ISSN: 1933-6926
PUBMED: 20009574
Abstract:
EGFR, a critical regulator of oncogenic signaling during cancer progression, is capable of integrating multireceptor signaling pathways that promote metastasis. EGFR is subject to regulatory cues from the extracellular matrix (ECM), of which hyaluronan (HA) is a major component. In mammary tumors, HA is deposited in the ECM where it functions in biomechanical support and modulates intracellular signaling. We utilized a 3D collagen system in which HA is either polymerized in collagen matrix or provided soluble in the media (sHA). Here we report that collagen-embedded HA (eHA) inhibits EGFR activation, filopodia formation and cell spreading on a collagen matrix. These findings demonstrate a novel role for eHA as a protective molecule when encountered in the collagen matrix during cancer progression.
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Cell Adh Migr 4(1): 26-31

Matrix hyaluronan alters epidermal growth factor receptor-dependent cell morphology

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Department of Molecular and Cellular Biology; and Arizona Cancer Center; Tucson, AZ USA
Bio5 Institute; The University of Arizona; AZ USA
Corresponding author.
Correspondence to: Joyce A. Schroeder; Email: ude.anozira.ccza@redeorhcsj
Correspondence to: Joyce A. Schroeder; Email: ude.anozira.ccza@redeorhcsj
Received 2009 Jul 18; Accepted 2009 Sep 29.

Abstract

EGFR, a critical regulator of oncogenic signaling during cancer progression, is capable of integrating multireceptor signaling pathways that promote metastasis. EGFR is subject to regulatory cues from the extracellular matrix (ECM), of which hyaluronan (HA) is a major component. In mammary tumors, HA is deposited in the ECM where it functions in biomechanical support and modulates intracellular signaling. We utilized a 3D collagen system in which HA is either polymerized in collagen matrix or provided soluble in the media (sHA). Here we report that collagen-embedded HA (eHA) inhibits EGFR activation, filopodia formation and cell spreading on a collagen matrix. These findings demonstrate a novel role for eHA as a protective molecule when encountered in the collagen matrix during cancer progression.

Keywords: HA, EGFR, collagen, extracellular matrix
Abstract

Acknowledgements

We are grateful to Ben Bitler, Matt Hart, and Matt Callan for a critical reading of this manuscript, and to Dave Bentley with the University Spectroscopy and Imagine Facilities at the University of Arizona. This work was supported by grants from the Arizona Biomedical Research Commission (J.A.S.), National Institutes of Health (J.A.S.), the Congressionally Directed Medical Research Programs and Department of Defense (J.M.V.L., J.I.L.) and Arizona Cancer Center Support Grant (J.A.S.).

Acknowledgements

Abbreviations

HAhyaluronan
ECMextracellular matrix
eHAembedded HA
sHAsoluble HA
Abbreviations

Footnotes

Previously published online: www.landesbioscience.com/journals/celladhesion/article/10252

Footnotes

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