Low colorectal tumor removal by E-cadherin destruction-enabled tumor cell dissociation
Low colorectal tumor removal by E-cadherin destruction-enabled tumor cell dissociation
复制标题
E-钙粘蛋白破坏导致肿瘤细胞解离，结直肠肿瘤去除率较低
DOI：
10.1021/acs.nanolett.1c04797
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发表时间：
2022
期刊：
影响因子：
10.8
通讯作者：
Jianlin Shi
中科院分区：
文献类型：
--
作者：
Man Li;Qunqun Bao;Jing Guo;Ruting Xie;Chao Shen;Qing Wei;Ping Hu;Huanlong Qin;Jianlin Shi
由于结肠造口带来的沉重的身体和心理负担、化疗中强烈的药物毒性以及骨髓抑制/放化疗相关的胃肠道症状，低位结直肠癌（CRC）的治疗仍然是一个巨大的挑战。在这项研究中，一种高度生物安全且有效的基于肿瘤细胞解离的低CRC治疗方式已在体外PDO和体内结直肠肿瘤模型上得到验证。值得注意的是，肿瘤部位的可控 EDTA 释放是通过响应低 CRC 肿瘤的微酸性微环境而降解 LDH 来实现的。结果，低CRC肿瘤细胞间连接的肿瘤内E-钙粘蛋白通过从层间释放的EDTA消耗Ca2+而被有效破坏，引发显着的肿瘤细胞解离并通过排便导致肿瘤解聚/去除。解离的肿瘤细胞普遍被LDH/EDTA包裹，这阻止了它们重新粘附到邻近组织，为低CRC提供了前所未有的、高效和安全的治疗方式，这将有利于患有低CRC的患者。
Treatments for low colorectal cancer (CRC) remain a great challenge due to the heavy physical and psychological burdens of colostomy, strong drug toxicity in chemotherapy, and myelosuppression-/chemoradiation-related gastrointestinal symptoms. In this study, a highly bio-safe and effective tumor cell dissociation-based low CRC treatment modality has been verified on both PDOs in vitro and colorectal tumor models in vivo. Notably, controllable EDTA release at the tumor sites was achieved by the LDH degradation in response to slightly acidic microenvironment of low CRC tumors. Resultantly, the intratumoral E-cadherin for intercellular junctions of low CRC tumors was effectively destroyed via Ca2+ depletion by released EDTA from the interlayers, initiating remarkable tumor cell dissociation and resultant tumor disaggregation/removal via defecation. Dissociated tumor cells were prevailingly enveloped by LDH/EDTA, which prevented them from re-adhering to adjacent tissues, providing an unprecedented, efficient and safe therapeutic modality for low CRC, which will benefit patients suffering low CRC.