Department of Molecular and Cellular Biology and Arizona Cancer Center, Tucson, AZ, USA.
Cell Adh Migr. 2010 Jan-Mar;4(1):26-31. doi: 10.4161/cam.4.1.10252. Epub 2010 Jan 29.
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.
表皮生长因子受体(EGFR)是肿瘤进展过程中致癌信号的关键调节因子,能够整合促进转移的多受体信号通路。EGFR 受到细胞外基质(ECM)的调节信号的影响,其中透明质酸(HA)是主要成分。在乳腺肿瘤中,HA 沉积在 ECM 中,在那里它起到生物力学支持和调节细胞内信号的作用。我们利用 3D 胶原系统,其中 HA 要么聚合在胶原基质中,要么以可溶性形式存在于培养基中(sHA)。在这里,我们报告说,胶原嵌入的 HA(eHA)抑制 EGFR 的激活、丝状伪足的形成和细胞在胶原基质上的铺展。这些发现表明,在癌症进展过程中遇到胶原基质时,eHA 作为一种保护分子具有新的作用。