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CXCR4-mediated adhesion and MMP-9 secretion in head and neck squamous cell carcinoma.

Abstract：

:The chemokine CXCL12 (SDF-1) and its receptor, CXCR4, have been implicated in organ-specific metastases of several malignancies. Head and neck squamous cell carcinoma (HNSCC) predominantly metastasizes to lymph nodes, and recent evidence has shown that CXCL12 stimulates HNSCC migration. We explored the potential role of CXCR4 in mediating other metastatic processes in HNSCC cells. CXCR4 mRNA and cell-surface expression was assessed in HNSCC cell lines. CXCR4 mRNA expression was detected in five HNSCC cell lines. Cell-surface CXCR4 was also detected in each of the HNSCC cell lines and in resected HNSCC tissues. CXCL12 induced rapid intracellular calcium mobilization in a metastatic HNSCC cell line (HN), as well as rapid phosphorylation of ERK-1/2. HNSCC cell adhesion to fibronectin and collagen was increased by CXCL12 treatment, while the addition of an inhibitor of ERK-1/2 signaling, PD98059, reduced the effects of CXCL12. CXCL12 also increased the active matrix metalloproteinase (MMP)-9 secreted. Thus, HNSCC cells express functional CXCR4 receptors that induce rapid intracellular signaling upon binding to CXCL12. Such binding leads to increased HNSCC cell adhesion and MMP secretion, suggesting that CXCR4 may be a novel regulator of HNSCC metastatic processes.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Samara GJ,Lawrence DM,Chiarelli CJ,Valentino MD,Lyubsky S,Zucker S,Vaday GG

doi

10.1016/j.canlet.2004.04.035

keywords:

subject

Has Abstract

pub_date

2004-10-28 00:00:00

pages

231-41

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(04)00372-6

journal_volume

214

pub_type

杂志文章

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