环境镉暴露在前列腺癌进展中的新作用

Rama Saad, Mohamed Ali Hussein, Gnanasekar Munirathinam, André Kajdacsy-Balla
{"title":"环境镉暴露在前列腺癌进展中的新作用","authors":"Rama Saad, Mohamed Ali Hussein, Gnanasekar Munirathinam, André Kajdacsy-Balla","doi":"10.3390/environments11080181","DOIUrl":null,"url":null,"abstract":"Cadmium (Cd) is a widespread environmental pollutant with several adverse effects on the general population. While Cd is a well-established risk factor for some cancers, such as lung cancer, its impact on prostate cancer (PCa) is not well understood. PCa mortality is associated with its progression to metastatic spread. This underscores the importance of studying the environmental/or molecular factors that govern the progression from organ-confined tumors to widely metastatic disease. To date, most studies addressing the effects of Cd on PCa are focused on the incidence rather than the progression/outcome. Furthermore, most of these epidemiological studies are limited by the small number of samples and the fact that most of these studies measured Cd levels in the air, blood, or urine, which is less applicable for addressing associations in environmental exposure than the measurement of Cd concentrations in the prostate microenvironment. It is still unknown whether Cd is a driver or a consequence of PCa aggressiveness. Addressing the plausibility of causality requires using proper in vitro and in vivo models for sub-micromolar Cd doses that mimic environmental exposure. Most in vitro studies addressing the functional and molecular effects of Cd are limited by the exclusive use of aggressive PCa cell models and very high micromolar unbound Cd concentrations, which are irrelevant for environmental exposure. Significantly, few studies have addressed the effects of sub-micromolar Cd concentrations. Hence, we suggest using nanomolar concentration that resembles real-life exposure, using less aggressive in vitro models such as RWPE-2, employing 3D organoid culture systems, and adopting high throughput-omics techniques, including metallomics, and using transgenic animal models might represent a more effective model. Here, we focus on reports on the impact of Cd on the progression and aggressiveness of already-established PCa instead of on the initial steps of carcinogenesis. We suggest potential future directions for substantiating the plausible link between Cd exposure and PCa aggressiveness.","PeriodicalId":11886,"journal":{"name":"Environments","volume":"1 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Emerging Role of Environmental Cadmium Exposure in Prostate Cancer Progression\",\"authors\":\"Rama Saad, Mohamed Ali Hussein, Gnanasekar Munirathinam, André Kajdacsy-Balla\",\"doi\":\"10.3390/environments11080181\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Cadmium (Cd) is a widespread environmental pollutant with several adverse effects on the general population. While Cd is a well-established risk factor for some cancers, such as lung cancer, its impact on prostate cancer (PCa) is not well understood. PCa mortality is associated with its progression to metastatic spread. This underscores the importance of studying the environmental/or molecular factors that govern the progression from organ-confined tumors to widely metastatic disease. To date, most studies addressing the effects of Cd on PCa are focused on the incidence rather than the progression/outcome. Furthermore, most of these epidemiological studies are limited by the small number of samples and the fact that most of these studies measured Cd levels in the air, blood, or urine, which is less applicable for addressing associations in environmental exposure than the measurement of Cd concentrations in the prostate microenvironment. It is still unknown whether Cd is a driver or a consequence of PCa aggressiveness. Addressing the plausibility of causality requires using proper in vitro and in vivo models for sub-micromolar Cd doses that mimic environmental exposure. Most in vitro studies addressing the functional and molecular effects of Cd are limited by the exclusive use of aggressive PCa cell models and very high micromolar unbound Cd concentrations, which are irrelevant for environmental exposure. Significantly, few studies have addressed the effects of sub-micromolar Cd concentrations. Hence, we suggest using nanomolar concentration that resembles real-life exposure, using less aggressive in vitro models such as RWPE-2, employing 3D organoid culture systems, and adopting high throughput-omics techniques, including metallomics, and using transgenic animal models might represent a more effective model. Here, we focus on reports on the impact of Cd on the progression and aggressiveness of already-established PCa instead of on the initial steps of carcinogenesis. We suggest potential future directions for substantiating the plausible link between Cd exposure and PCa aggressiveness.\",\"PeriodicalId\":11886,\"journal\":{\"name\":\"Environments\",\"volume\":\"1 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Environments\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/environments11080181\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Environments","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/environments11080181","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

镉(Cd)是一种广泛存在的环境污染物,对普通人群有多种不利影响。虽然镉是某些癌症(如肺癌)的公认风险因素,但它对前列腺癌(PCa)的影响却不甚了解。PCa 的死亡率与其转移扩散的进展有关。这凸显了研究从器官局限性肿瘤发展为广泛转移性疾病的环境/或分子因素的重要性。迄今为止,大多数有关镉对 PCa 影响的研究都侧重于发病率而非进展/结果。此外,这些流行病学研究大多受到样本数量少的限制,而且这些研究大多测量的是空气、血液或尿液中的镉含量,这与测量前列腺微环境中的镉浓度相比,更不适用于研究环境暴露中的相关性。目前还不清楚镉是 PCa 侵袭性的驱动因素还是结果。要解决因果关系的合理性问题,需要使用适当的体外和体内模型来模拟环境接触的亚微摩镉剂量。大多数涉及镉的功能和分子效应的体外研究都受到了限制,因为它们只使用了侵袭性 PCa 细胞模型和极高的微摩尔非结合镉浓度,这与环境暴露无关。值得注意的是,很少有研究涉及亚微摩尔浓度镉的影响。因此,我们建议使用纳摩尔浓度(类似于真实生活中的暴露)、使用侵袭性较低的体外模型(如 RWPE-2)、采用三维类器官培养系统、采用高通量组学技术(包括金属组学)以及使用转基因动物模型可能是更有效的模型。在此,我们重点关注有关镉对已形成的 PCa 的进展和侵袭性的影响的报告,而不是对致癌初始步骤的影响。我们为证实镉暴露与 PCa 侵袭性之间的合理联系提出了潜在的未来方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Emerging Role of Environmental Cadmium Exposure in Prostate Cancer Progression
Cadmium (Cd) is a widespread environmental pollutant with several adverse effects on the general population. While Cd is a well-established risk factor for some cancers, such as lung cancer, its impact on prostate cancer (PCa) is not well understood. PCa mortality is associated with its progression to metastatic spread. This underscores the importance of studying the environmental/or molecular factors that govern the progression from organ-confined tumors to widely metastatic disease. To date, most studies addressing the effects of Cd on PCa are focused on the incidence rather than the progression/outcome. Furthermore, most of these epidemiological studies are limited by the small number of samples and the fact that most of these studies measured Cd levels in the air, blood, or urine, which is less applicable for addressing associations in environmental exposure than the measurement of Cd concentrations in the prostate microenvironment. It is still unknown whether Cd is a driver or a consequence of PCa aggressiveness. Addressing the plausibility of causality requires using proper in vitro and in vivo models for sub-micromolar Cd doses that mimic environmental exposure. Most in vitro studies addressing the functional and molecular effects of Cd are limited by the exclusive use of aggressive PCa cell models and very high micromolar unbound Cd concentrations, which are irrelevant for environmental exposure. Significantly, few studies have addressed the effects of sub-micromolar Cd concentrations. Hence, we suggest using nanomolar concentration that resembles real-life exposure, using less aggressive in vitro models such as RWPE-2, employing 3D organoid culture systems, and adopting high throughput-omics techniques, including metallomics, and using transgenic animal models might represent a more effective model. Here, we focus on reports on the impact of Cd on the progression and aggressiveness of already-established PCa instead of on the initial steps of carcinogenesis. We suggest potential future directions for substantiating the plausible link between Cd exposure and PCa aggressiveness.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信