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题目:: VEGFR-1 expressed by malignant melanoma initiating cells is required for tumor growth
ID:
状态:: 发布时间Jan. 13, 2011 , 更新时间 March 27, 2012
物种:: Homo sapiens
摘要:: Melanoma growth is driven by malignant melanoma initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member, ABCB5. ABCB5+ melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE-1 and are associated with CD31-negative vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5+ MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5+ tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced in a VEGFR-1-dependent manner expression of CD144 in ABCB5+ subpopulations that constitutively expressed VEGFR-1, but not in ABCB5- bulk populations that were predominantly VEGFR-1-negative. In vivo, melanomaspecific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5+ VM morphology and inhibited ABCB5+ VM-associated production of the secreted melanoma mitogen, laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results demonstrate that VEGFR-1 function in MMIC regulates VM and associated laminin production, and show that this function represents one mechanism through which MMIC promote tumor growth. Microarray analyses were performed on purified ABCB5+ (n=5) and ABCB5- (n=5) cell subsets derived from the established human melanoma cell lines G3361 and A375 and from three distinct clinical melanoma specimen. Total RNA was extracted, processed and hybridized onto Affymetrix human HG-U133Plus2 GeneChip microarrays (Affymetrix, Santa Clara, CA).
实验种类:: transcription profiling by array
样本量:: 10
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: 无设计数据
数据号:: E-GEOD-26569, GSE26569
数据状态:: 无法自动分析，您可以尝试手动分析数据。

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