RRC ID 42904
著者 Zhang L, Yeger H, Das B, Irwin MS, Baruchel S.
タイトル Tissue microenvironment modulates CXCR4 expression and tumor metastasis in neuroblastoma.
ジャーナル Neoplasia
Abstract Neuroblastoma (NB) is derived from intrinsic migratory neural crest cells and has a high potential for distant metastasis. Growing evidence has implicated chemokine receptors, especially CXCR4, which normally control immune and inflammatory cell migration, as having important roles in tumor progression. In this study, we investigated the expression of CXCR4 in eight different NB cell lines and found that CXCR4 expression is dynamically regulated in NB and can be modulated by different tissue stromata. In addition, we demonstrate that IL-5 and IFN-gamma are released from stromal cells and act as differential mediators for CXCR4 expression. We also overexpressed CXCR4 in two NB cell lines, NUB-7 and SK-N-BE(2), and studied the role of CXCR4 in NB metastasis both in vitro and in vivo. In vitro transwell invasion assay showed that CXCR4 overexpression promoted NB cell migration preferentially toward a bone marrow stromal cell-conditioned medium. Using an in vivo xenograft model, CXCR4-overexpressing cells showed an increased incidence of metastasis, most notably bone marrow metastasis. Our studies reveal critical roles for CXCR4 in NB metastasis and provide insights into the regulatory mechanism of chemokine receptors in NB and the importance of the tissue microenvironment in modulating tumor cell behavior.
巻・号 9(1)
ページ 36-46
公開日 2007-1-1
DOI 10.1593/neo.06670
PMID 17325742
PMC PMC1803034
MeSH Animals Cell Line, Tumor Humans Interferon-gamma / physiology Interleukin-5 / physiology Mice Mice, SCID Neoplasm Invasiveness Neoplasm Metastasis Neoplasm Transplantation Neuroblastoma / pathology* RNA, Messenger / analysis Receptors, CXCR4 / analysis Receptors, CXCR4 / genetics Receptors, CXCR4 / physiology*
IF 5.696
引用数 60
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 GOTO·P3(RCB0721)