Roles of HIF-1α in a novel optical orthotopic spontaneous metastatic bladder cancer animal model
Roles of HIF-1α in a novel optical orthotopic spontaneous metastatic bladder cancer animal model
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DOI：
10.1016/j.urolonc.2012.01.003
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发表时间：
2012-11-01
影响因子：
2.7
通讯作者：
He, Dalin
中科院分区：
文献类型：
--
作者：
Zhang, Tingting;Fan, Jinhai;He, Dalin
尽管转移性疾病在大多数膀胱癌病例中是致命的，但对该过程的分子机制的研究受到远处转移肿瘤组织来源有限和合适的动物模型很少的影响。为了满足这一需求，我们通过将人膀胱癌T24致瘤（T24-t）细胞滴注到小鼠膀胱中来生成原位动物模型，随后衍生出亚系作为原发（T24-亲本，T24-P）和肺转移（T24-L）位点。侵袭、迁移和粘附测定的数据表明，T24-L 细胞的体外转移潜力高于 T24-P 细胞。使用两种转移模型评估体内转移能力，T24-L细胞表现出较高的肿瘤转移发生率。从机制上讲，在 T24-L 细胞中观察到 MMP-1 和 HIF-1 α 的上调。敲低HIF-1α可显着下调MMP-1的表达，并伴有体外侵袭能力下降。使用免疫组织化学染色，我们进一步观察到与同一患者的原发性膀胱癌组织相比，转移性淋巴瘤组织中的 HIF-1 α 升高。综上所述，我们的研究证明了 HIF-1 α/MMP-1 在调节膀胱癌转移中的功能，以及 HIF-1 α 作为控制膀胱癌转移的潜在靶点。 (C) 2012 年，爱思唯尔公司出版。
Although metastatic disease is lethal in the majority of bladder cancer cases, study on the molecular mechanism(s) of this process suffers from the limited source of distant metastatic tumor tissues and very few suitable animal models. To address this need, we generated an orthotopic animal model by instilling human bladder cancer T24-tumorigenic (T24-t) cells into mouse bladder, and sublines were subsequently derived as primary (T24-parental, T24-P) and lung metastatic (T24-L) sites. Data from invasion, migration, and adhesion assays suggested higher metastatic potential of T24-L cells than T24-P cells in vitro. Using two metastatic models to assess the metastatic ability in vivo, T24-L cells exhibited higher incidence of tumor metastasis. Mechanistically, the up-regulation of MMP-1 and HIF-1 alpha was observed in T24-L cells. Knocking down HIF-1 alpha can significantly down-regulate the expression of MMP-1, accompanied by the decreased invasion ability in vitro. Using immunohistochemical staining, we further observed HIF-1 alpha elevation in the metastatic lymphomatic tissues compared with the primary bladder cancer tissues from the same patients. Taken together, our study provides the evident of the function of HIF-1 alpha/MMP-1 in regulating metastasis of bladder cancer and HIF-1 alpha as a potential target for controlling bladder cancer metastasis. (C) 2012 Published by Elsevier Inc.