Adrenomedullin在表浅性膀胱癌复发中的作用及机制——基于血管内皮细胞介导的化疗后肿瘤生长的研究

Tendency to recur is one of the obstacles for superficial bladder cancer treatment.Chemoresistant cancer cells probably provide the main sources of recurrent tumors.In recent years,we focus on the mechanisms by which these chemoresistant cells develop into recurrent tumors and found that aquired chemoresistance enhance recruitment of endothelial cells by tumor cells,and that the recruited endothelial cells facilitated the growth of chemoresistant bladder cancer cells and contribute to bladder cancer recurrence after chemotherapy. Based on this,we found that the expression of proagiogenic factor adrenomedullin was increased in chemoresistant bladder cancer cells and recurrent tumors after intravesical chemotherapy.Thus, we hypothesize that adrenomedullin may play a crucial role on bladder cancer recurrence after chemotherapy. Our study focus on the relationship of adrenomedullin expression and bladder cancer recurrence after chemotherapy,and the role of adrenomedullin meidated agiogenesis and tumor cell-endothelial cell interplay on the growth of chemoresistant cells，in order to investigate the role and mechanism of adrenomedullin on bladder cancer recurrence after chemotherapy,and the possibility of adrenomedullin as a potential therapeutic target for reducing superficial bladder cancer recurrence.

高复发率是表浅性膀胱癌临床治疗的重要难题，化疗耐药细胞则被认为是其治疗后复发的重要细胞来源。近年来，我们基于膀胱癌细胞在获得耐药后如何生长成复发肿瘤这一问题展开研究，发现膀胱癌细胞在获得耐药的同时也获得了对血管内皮细胞的招募能力并通过血管内皮细胞促进耐药细胞的生长和肿瘤复发。在此基础上，我们通过预实验发现促血管生长因子adrenomedullin在表浅性膀胱癌化疗后复发标本及膀胱癌耐药细胞株表达明显上调。因此我们推测adrenomedullin可能在膀胱癌化疗后复发方面扮演着重要角色。本研究拟通过观察adrenomedullin与膀胱癌化疗预后的关系以及adrenomedullin介导的血管形成及肿瘤细胞-内皮细胞相互作用对耐药细胞生长的影响来探讨adrenomedullin在膀胱癌化疗后复发中的作用及相关机制，以及adrenomedullin作为治疗靶点用于降低表浅性膀胱癌复发的可能性。

高复发率是表浅性膀胱癌临床治疗的重要难题，化疗耐药细胞则被认为是其治疗后复发的重要细胞来源。在本研究中，我们基于膀胱癌细胞在获得耐药后如何生长成复发肿瘤这一问题展开研究，发现以adrenomedullin为代表的促血管生长因子在耐药细胞表达上调，进而招募血管内皮细胞至肿瘤部位。而进入肿瘤微环境中的血管内皮细胞一方面可促进血管形成，另一方面可直接促进耐药肿瘤细胞生长。我们的研究表明，化疗后由耐药细胞启动的肿瘤细胞-血管内皮细胞相互作用在膀胱癌复发中发挥了重要作用。