Impact of prospero homeobox-1 on tumor cell behavior and prognosis in colorectal cancer.
Impact of prospero homeobox-1 on tumor cell behavior and prognosis in colorectal cancer.
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发表时间：
2015-10
影响因子：
5.3
通讯作者：
Young‐Lan Park;Eun Myung;Sun-Young Park;Nuri Kim;C. Oak;D. Myung;Sung-Bum Cho;Wan-Sik Lee;S. Kweon;Hyun-Soo Kim;Y. Joo
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作者：
Young‐Lan Park;Eun Myung;Sun-Young Park;Nuri Kim;C. Oak;D. Myung;Sung-Bum Cho;Wan-Sik Lee;S. Kweon;Hyun-Soo Kim;Y. Joo
Prospero同源框1（PROX 1）在结直肠癌中上调，并发挥致癌作用。在本研究中，我们试图研究PROX 1对致癌过程的影响，并评估PROX 1表达在结直肠癌中的预后价值。应用小分子干扰RNA（siRNA）或pcDNA 6-myc载体对大肠癌细胞株DLD 1和SW 480中PROX 1基因的表达进行调控。采用免疫组化方法检测PROX 1在大肠癌组织中的表达。免疫组化染色后，通过分析这些现象的相应标志物CD 34、D2-40和Ki-67的表达来评估血管生成、淋巴管生成和肿瘤细胞增殖。PROX 1基因敲低可降低脐静脉内皮细胞的侵袭能力和管腔形成，下调VEGF-A和HIF-1α的表达，上调Angiostatin的表达。PROX 1基因敲低还可抑制淋巴管内皮细胞的浸润和管腔形成以及VEGF-C的表达。PROX 1敲低抑制肿瘤细胞增殖、迁移、侵袭和上皮-间质转化。相反，PROX 1过表达增强肿瘤细胞血管生成、淋巴管生成、增殖、迁移、侵袭和上皮-间质转化。磷酸化Akt、GSK 3 β和MAPK的水平在PROX 1敲低时降低，在PROX 1过表达时升高。PROX 1表达与肿瘤大小、分化程度、淋巴管浸润、浸润深度、淋巴结转移、分期和生存率相关。PROX 1阳性肿瘤的平均微血管密度和Ki-67标记指数值显著高于PROX 1阴性肿瘤。而PROX 1的表达与淋巴管密度无明显相关性。这些结果表明，PROX 1通过调节血管生成和肿瘤细胞增殖来影响结直肠癌的肿瘤进展。
Prospero homeobox 1 (PROX1) is up-regulated in colorectal cancer and plays an oncogenic role. In the present study, we sought to investigate the impact of PROX1 on oncogenic processes and to assess the prognostic value of PROX1 expression in colorectal cancer. A small interfering RNA or pcDNA6-myc vector was used to control PROX1 gene expression in colorectal cancer DLD1 and SW480 cell lines. The expression of PROX1 in colorectal cancer tissues was investigated by immunohistochemistry. Angiogenesis, lymphangiogenesis, and tumor cell proliferation were assessed by analyzing the expression of respective markers of these phenomena, CD34, D2-40, and Ki-67 after immunohistochemical staining. PROX1 knockdown decreased both umbilical vein endothelial cell invasion and tube formation, down-regulated the expression of VEGF-A and HIF-1α, and up-regulated the expression of angiostatin. Lymphatic endothelial cell invasion and tube formation as well as the expression of VEGF-C were also suppressed by PROX1 knockdown. PROX1 knockdown suppressed tumor cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In contrast, PROX1 overexpression enhanced tumor cell angiogenesis, lymphangiogenesis, proliferation, migration, invasion, and epithelial-mesenchymal transition. Levels of phosphorylated Akt, GSK3β, and MAPK were decreased by PROX1 knockdown and increased by PROX1 overexpression. PROX1 expression positively correlated with tumor size, extent of differentiation, lymphovascular invasion, depth of invasion, lymph node metastasis, stage, and poor survival. The mean microvessel density and Ki-67 labeling index values of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, there was no significant correlation between PROX1 expression and lymphatic vessel density. These results indicate that PROX1 influences tumor progression in colorectal cancer by regulating angiogenesis and tumor cell proliferation.