FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence
FGF2-mediated reciprocal tumor cell-endothelial cell interplay contributes to the growth of chemoresistant cells: a potential mechanism for superficial bladder cancer recurrence
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FGF2介导的肿瘤细胞-内皮细胞相互作用促进化疗耐药细胞的生长：浅表性膀胱癌复发的潜在机制
DOI：
10.1007/s13277-015-4214-4
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发表时间：
2016-04-01
期刊：
影响因子：
--
通讯作者：
He, Dalin
中科院分区：
文献类型：
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作者：
Chen, Yule;Zhu, Guodong;He, Dalin
浅表性膀胱癌患者可以通过一次经尿道电切术(TUR)加额外的膀胱内化疗而最终治愈；然而，高达75%的患者表现出频繁和多次复发。复发的主要原因之一是在膀胱内化疗方案中使用的化疗药物可能导致化疗耐药。然而，这些化疗耐药细胞发展成复发肿瘤的机制尚不清楚。最近的临床证据表明，促血管生成因子FGF2的表达与浅表性膀胱癌患者早期局部复发有关。在本研究中，我们对化疗耐药细胞介导膀胱癌复发的机制进行了初步探讨，重点是FGF2启动的肿瘤细胞-内皮细胞相互作用对化疗耐药癌细胞生长的影响。我们发现，FGF2在化疗耐药的膀胱细胞系和膀胱组织中的表达增加。尽管耐化疗的膀胱癌细胞生长慢于亲本细胞，但耐化疗的膀胱癌细胞比亲本细胞有更强的能力通过产生FGF2刺激内皮细胞迁移、生长和管状形成。相反，血管内皮细胞在体外和体内都显著促进了耐药膀胱癌的生长。因此，靶向化疗诱导的FGF2上调可能为控制浅表性膀胱癌的复发提供了一种有前途的方法。
Patients with superficial bladder cancer can be definitively cured by one single transurethral resection (TUR) with additional intravesical chemotherapy; however, up to 75 % of cases display frequent and multiple recurrences. One of the major causes of recurrence is that chemotherapeutic drugs used in intravesical regimens may induce chemoresistance. However, the mechanisms by which these chemoresistant cells develop into recurrent tumors remain unclear. Recent clinical evidence revealed that the expression of pro-angiogenic factor FGF2 was associated with early local relapse in patients with superficial bladder cancer. In this study, we conducted a preliminary investigation of the mechanisms of chemoresistant cells mediated bladder cancer recurrence, focusing on FGF2-initiated tumor cell-endothelial cell interaction on chemoresistant cancer cell growth. We found that the expression of FGF2 was increased in chemoresistant bladder cell lines and in bladder tissues after intravesical chemotherapy. Although chemoresistant bladder cells grow slower than parental cells, chemoresistant bladder cancer cells had stronger ability than parental cells to stimulate endothelial cell migration, growth, and tube formation by producing FGF2. Inversely, endothelial cells significantly promoted chemoresistant bladder cancer growth in vitro and in vivo. Thus, targeting chemotherapy-induced FGF2 upregulation may provide a promising approach to manage the recurrence of superficial bladder cancer.