Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations.
Comparing the Secretomes of Chemorefractory and Chemoresistant Ovarian Cancer Cell Populations.
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DOI：
10.3390/cancers14061418
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发表时间：
2022-03-10
期刊：
影响因子：
5.2
通讯作者：
Dawson MR
中科院分区：
文献类型：
--
作者：
Lee AH;Mejia Peña C;Dawson MR
上皮性卵巢癌（EOC）是一种妇科疾病，由于其异质性以及许多女性对各种治疗策略产生耐药性，治疗起来很复杂。肿瘤复发可以通过双管齐下的方法进行检查：多次接触一线抗癌药物后产生的耐药性，或因缺氧等不良微环境条件而产生的耐药性。尽管有多种方法可以赋予化学抗性，但研究表明，化学抗性 EOC 细胞释放独特的分泌组谱，包括细胞因子、生长因子和细胞外囊泡 (EV)。这些分泌的因子激活细胞内途径，从而导致化疗耐药。分泌的 EV 将生物材料（包括蛋白质、RNA 和 microRNA）转移到其他细胞，这对于细胞间的通讯至关重要；因此，EV 含量的变化，特别是外泌体 miRNA，已被用来预测 EOC 预后。这篇综述研究了反馈循环，其中化学抗性 EOC 细胞释放独特的分泌组谱，赋予正常旁观细胞和癌细胞化学抗性。高级别浆液性卵巢癌 (HGSOC) 占所有卵巢癌病例的大多数，其难治性和复发性疾病的发病率惊人。虽然大多数患者对紫杉醇和铂类药物的初始治疗有反应，但高达 25% 的患者没有反应，而在剩下的有反应的患者中，75% 的患者在随后的两年内出现疾病复发。难治性病例的内在耐药性是由肿瘤缺氧等环境应激源驱动的，这些环境应激源会改变肿瘤微环境，从而促进癌症进展和抗癌药物耐药性。复发性疾病描述了化疗耐药性的获得，癌细胞在最初的化疗中存活下来，并发展适应以提高其在后续治疗中存活的机会。在癌细胞所承受的环境压力中，暴露于缺氧已被确定为化学抗性发展的有效触发剂和启动剂。无论是在缺氧压力还是化疗治疗压力的情况下，癌细胞都能设法应对并发展出适应能力，从而使细胞群能够在未来的压力下生存。一种适应是分泌蛋白组的修饰。化学抗性与增加蛋白质合成、核糖体生物发生和囊泡运输的翻译重编程有关。这导致参与自分泌和旁分泌信号传导过程的可溶性蛋白质和细胞外囊泡 (EV) 的产生增加。大量研究表明，这些因素在化疗敏感和化疗耐药患者的分泌蛋白组之间发生很大变化。这些因子包括细胞因子、生长因子、EV 和 EV 封装的 microRNA (miRNA)，它们可在邻近的正常细胞和癌细胞中诱导侵袭性分子、生物物理和化学抗性表型。本综述检查了不同化疗耐药性卵巢癌细胞群和特定分泌因子的分泌组的修饰，这些修饰可作为侵袭性和化疗耐药性癌症的候选生物标志物。
Epithelial ovarian cancer (EOC) is a gynecological disease that is complicated to treat due to its heterogenous nature and because many women develop resistance to various therapeutic strategies. Tumor recurrence can be examined as a two-pronged approach: resistance developed after multiple exposures to frontline anticancer drugs or resistance developed in response to poor microenvironmental conditions, such as hypoxia. Although there are numerous ways to confer chemoresistance, studies have shown that chemoresistant EOC cells release unique secretome profiles that include cytokines, growth factors, and extracellular vesicles (EVs). These secreted factors activate intracellular pathways that contribute to chemoresistance. Secreted EVs transfer biomaterials (including proteins, RNAs, and microRNAs) to other cells, which is critical in cell–cell communication; thus, changes in EV content, in particular exosome miRNAs, have been used to project EOC prognosis. This review examines the feedback loop where chemoresistant EOC cells release unique secretome profiles that confer chemoresistance in normal bystander cells and cancer cells. High-grade serous ovarian cancer (HGSOC) constitutes the majority of all ovarian cancer cases and has staggering rates of both refractory and recurrent disease. While most patients respond to the initial treatment with paclitaxel and platinum-based drugs, up to 25% do not, and of the remaining that do, 75% experience disease recurrence within the subsequent two years. Intrinsic resistance in refractory cases is driven by environmental stressors like tumor hypoxia which alter the tumor microenvironment to promote cancer progression and resistance to anticancer drugs. Recurrent disease describes the acquisition of chemoresistance whereby cancer cells survive the initial exposure to chemotherapy and develop adaptations to enhance their chances of surviving subsequent treatments. Of the environmental stressors cancer cells endure, exposure to hypoxia has been identified as a potent trigger and priming agent for the development of chemoresistance. Both in the presence of the stress of hypoxia or the therapeutic stress of chemotherapy, cancer cells manage to cope and develop adaptations which prime populations to survive in future stress. One adaptation is the modification in the secretome. Chemoresistance is associated with translational reprogramming for increased protein synthesis, ribosome biogenesis, and vesicle trafficking. This leads to increased production of soluble proteins and extracellular vesicles (EVs) involved in autocrine and paracrine signaling processes. Numerous studies have demonstrated that these factors are largely altered between the secretomes of chemosensitive and chemoresistant patients. Such factors include cytokines, growth factors, EVs, and EV-encapsulated microRNAs (miRNAs), which serve to induce invasive molecular, biophysical, and chemoresistant phenotypes in neighboring normal and cancer cells. This review examines the modifications in the secretome of distinct chemoresistant ovarian cancer cell populations and specific secreted factors, which may serve as candidate biomarkers for aggressive and chemoresistant cancers.
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影响因子：
4.7
作者：
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影响因子：
5.2
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