The Diverse Roles of Heme Oxygenase-1 in Tumor Progression.
The Diverse Roles of Heme Oxygenase-1 in Tumor Progression.
复制标题
DOI：
10.3389/fimmu.2021.658315
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Arnold JN
中科院分区：
文献类型：
--
作者：
Luu Hoang KN;Anstee JE;Arnold JN
血红素加氧酶-1 （HO-1）是一种可诱导的细胞内酶，在多种刺激下表达以降解血红素，产生具有生物活性的分解产物一氧化碳（CO）、胆绿素和亚铁（Fe2+）。HO-1在多种癌症中表达，并已被证明通过多种机制促进肿瘤进展。HO-1可以在肿瘤微环境（tumor microenvironment， TME）内的多种细胞中表达，既包括恶性肿瘤细胞，也包括巨噬细胞、树突状细胞和调节性t细胞等基质细胞群。在细胞内部，HO-1活性通过其分解代谢物提供抗氧化、抗凋亡和细胞保护作用，并清除有毒的细胞内血红素。然而，血红素降解的分解代谢物也可以扩散到细胞外，从外部调节更广泛的TME，影响细胞功能和促进肿瘤进展的生物学过程，如促进血管生成和转移，以及促进抗炎症和免疫抑制。药理抑制HO-1已被证明是促进抗肿瘤免疫反应和抑制肿瘤转移的一种有前景的治疗方法。然而，这些生物学功能可能与环境、TME和细胞类型有关，因为HO-1活性促进抗肿瘤过程的报道也存在冲突。这篇综述将考虑我们目前对HO-1在癌症进展中的作用和作为癌症治疗靶点的理解。
Heme oxygenase-1 (HO-1) is an inducible intracellular enzyme that is expressed in response to a variety of stimuli to degrade heme, which generates the biologically active catabolites carbon monoxide (CO), biliverdin and ferrous iron (Fe2+). HO-1 is expressed across a range of cancers and has been demonstrated to promote tumor progression through a variety of mechanisms. HO-1 can be expressed in a variety of cells within the tumor microenvironment (TME), including both the malignant tumor cells as well as stromal cell populations such as macrophages, dendritic cells and regulatory T-cells. Intrinsically to the cell, HO-1 activity provides antioxidant, anti-apoptotic and cytoprotective effects via its catabolites as well as clearing toxic intracellular heme. However, the catabolites of heme degradation can also diffuse outside of the cell to extrinsically modulate the wider TME, influencing cellular functionality and biological processes which promote tumor progression, such as facilitating angiogenesis and metastasis, as well as promoting anti-inflammation and immune suppression. Pharmacological inhibition of HO-1 has been demonstrated to be a promising therapeutic approach to promote anti-tumor immune responses and inhibit metastasis. However, these biological functions might be context, TME and cell type-dependent as there is also conflicting reports for HO-1 activity facilitating anti-tumoral processes. This review will consider our current understanding of the role of HO-1 in cancer progression and as a therapeutic target in cancer.
登录
查看更多内容
DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Casares N;Pequignot MO;Tesniere A;Ghiringhelli F;Roux S;Chaput N;Schmitt E;Hamai A;Hervas-Stubbs S;Obeid M;Coutant F;Métivier D;Pichard E;Aucouturier P;Pierron G;Garrido C;Zitvogel L;Kroemer G
通讯作者：
Kroemer G
影响因子：
11.5
作者：
Berberat, PO;Dambrauskas, Z;Friess, H
通讯作者：
Friess, H
影响因子：
4.8
作者：
Choi, Yoon Kyung;Kim, Chun-Ki;Kim, Young-Myeong
通讯作者：
Kim, Young-Myeong
影响因子：
3.6
作者：
Carolina Andres, Nancy;Eugenia Fermento, Maria;Marta Facchinetti, Maria
通讯作者：
Marta Facchinetti, Maria
影响因子：
4.8
作者：
Bindu, Samik;Pal, Chinmay;Bandyopadhyay, Uday
通讯作者：
Bandyopadhyay, Uday