Matrix hyaluronan alters epidermal growth factor receptor-dependent cell morphology.
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.
Louderbough
Jeanne M V
JM
Department of Molecular and Cellular Biology and Arizona Cancer Center, Tucson, AZ, USA.
Lopez
Jose I
JI
Schroeder
Joyce A
JA
D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D002465:Cell Movement; D048430:Cell Shape; D024042:Collagen Type I / Q000378:metabolism; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats
D024042:Collagen Type I; D006820:Hyaluronic Acid; D066246:ErbB Receptors