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Liu J, Lu J, Wu L, Zhang T, Wu J, Li L, Tai Z, Chen Z, Zhu Q. Targeting tumor-associated macrophages: Novel insights into immunotherapy of skin cancer. J Adv Res 2025; 67:231-252. [PMID: 38242529 PMCID: PMC11725115 DOI: 10.1016/j.jare.2024.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/19/2023] [Accepted: 01/11/2024] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND The incidence of skin cancer is currently increasing, and conventional treatment options inadequately address the demands of disease management. Fortunately, the recent rapid advancement of immunotherapy, particularly immune checkpoint inhibitors (ICIs), has ushered in a new era for numerous cancer patients. However, the efficacy of immunotherapy remains suboptimal due to the impact of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs), a major component of the TME, play crucial roles in tumor invasion, metastasis, angiogenesis, and immune evasion, significantly impacting tumor development. Consequently, TAMs have gained considerable attention in recent years, and their roles have been extensively studied in various tumors. However, the specific roles of TAMs and their regulatory mechanisms in skin cancer remain unclear. AIM OF REVIEW This paper aims to elucidate the origin and classification of TAMs, investigate the interactions between TAMs and various immune cells, comprehensively understand the precise mechanisms by which TAMs contribute to the pathogenesis of different types of skin cancer, and finally discuss current strategies for targeting TAMs in the treatment of skin cancer. KEY SCIENTIFIC CONCEPTS OF OVERVIEW With a specific emphasis on the interrelationship between TAMs and skin cancer, this paper posits that therapeutic modalities centered on TAMs hold promise in augmenting and harmonizing with prevailing clinical interventions for skin cancer, thereby charting a novel trajectory for advancing the landscape of immunotherapeutic approaches for skin cancer.
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Affiliation(s)
- Jun Liu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China
| | - Jiaye Lu
- School of Medicine, Shanghai University, 99 Shangda Road, Shanghai 200444, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China
| | - Ling Wu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China
| | - Tingrui Zhang
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China
| | - Junchao Wu
- School of Medicine, Shanghai University, 99 Shangda Road, Shanghai 200444, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China
| | - Lisha Li
- School of Medicine, Shanghai University, 99 Shangda Road, Shanghai 200444, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China
| | - Zongguang Tai
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China.
| | - Zhongjian Chen
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China.
| | - Quangang Zhu
- Shanghai Skin Disease Hospital, School of Medicine, Tongji University, 1278 Baode Road, Shanghai 200443, China; Shanghai Engineering Research Center of Topical Chinese Medicine, 1278 Baode Road, Shanghai 200443, China.
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Ji WT, Cui CG, Wang Y. EAF2: a tumor suppressor gene with multi-aspect functions. Front Pharmacol 2024; 15:1440511. [PMID: 39588149 PMCID: PMC11586179 DOI: 10.3389/fphar.2024.1440511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 10/30/2024] [Indexed: 11/27/2024] Open
Abstract
Since ELL-associated factor 2 (EAF2) was identified in 1997 as an androgen response gene, it has been of medical and scientific interest. Early studies demonstrated the tumor-suppressing function of EAF2 in the prostate. Sequencing studies indicated an association between EAF2 and several other malignant diseases and multiple physiological processes, such as transcription, apoptosis, embryogenesis, and DNA repair. Further understanding of EAF2 will provide new opportunities and therapeutic approaches for cancers, especially prostate cancer. This narrative review summarizes the existing knowledge of EAF2 and outlines its potential significance. To our knowledge, this is the first review of the role of this novel tumor suppressor gene and its possible functions.
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Affiliation(s)
- Wen-Tong Ji
- Urology 2nd Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Chun-Guo Cui
- Galactophore Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Yao Wang
- Urology 2nd Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
- Jilin Key Laboratory of Molecular Diagnosis of Urologic Neoplasms, Urology 2nd Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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Cong L, Zhao Q, Sun H, Zhou Z, Hu Y, Li C, Hao M, Cong X. A novel long non-coding RNA SLNCR1 promotes proliferation, migration, and invasion of melanoma via transcriptionally regulating SOX5. Cell Death Discov 2024; 10:160. [PMID: 38561355 PMCID: PMC10984963 DOI: 10.1038/s41420-024-01922-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 03/13/2024] [Accepted: 03/19/2024] [Indexed: 04/04/2024] Open
Abstract
Steroid receptor RNA activator (SRA)-like non-coding RNA (SLNCR1) has been implicated in various tumorigenic processes, but the precise regulatory role in melanoma progression remains uncertain. We performed a comprehensive analysis to investigate the prognostic value of SLNCR1 expression in patients with melanoma by TCGA database and melanoma tissue samples via the Kaplan-Meier method. Subsequently, we conducted qRT-PCR and Fluorescence in Situ Hybridization (FISH) assays to identify SLNCR1 expression levels and localization in tissues and cells, respectively. Loss-of-function assays utilizing shRNAs vectors were used to investigate the potential impact of SLNCR1. Our data showed that SLNCR1 is significantly up-regulated in human malignant melanoma tissues and cell lines and functions as an oncogene. Silencing of SLNCR1 suppressed melanoma cell proliferation, migration, invasion, and inhibited tumorigenesis in a mouse xenograft model. Additionally, we employed bioinformatic predictive analysis, combined with dual-luciferase reporter analysis and functional rescue assays, to elucidate the mechanistic target of the SLNCR1/SOX5 axis in melanoma. Mechanistically, we discovered that SLNCR1 promotes EMT of human melanoma by targeting SOX5, as downregulation of SLNCR1 expression leads to a decrease in SOX5 protein levels and inhibits melanoma tumorigenesis. Our research offers promising insights for more precise diagnosis and treatment of human melanoma.
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Affiliation(s)
- Lele Cong
- Department of Dermatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Qing Zhao
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Hongyan Sun
- Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Zilong Zhou
- Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Yue Hu
- Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
| | - Chunyi Li
- Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun, China
| | - Miao Hao
- Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
| | - Xianling Cong
- Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
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Feng ML, Sun MJ, Xu BY, Liu MY, Zhang HJ, Wu C. Mechanism of ELL-associated factor 2 and vasohibin 1 regulating invasion, migration, and angiogenesis in colorectal cancer. World J Gastroenterol 2023; 29:3770-3792. [PMID: 37426316 PMCID: PMC10324531 DOI: 10.3748/wjg.v29.i24.3770] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/08/2023] [Accepted: 05/12/2023] [Indexed: 06/28/2023] Open
Abstract
BACKGROUND As a novel endogenous anti-angiogenic molecule, vasohibin 1 (VASH1) is not only expressed in tumor stroma, but also in tumor tissue. Moreover, studies have shown that VASH1 may be a prognostic marker in colorectal cancer (CRC). Knockdown of VASH1 enhanced transforming growth factor-β1 (TGF-β1)/Smad3 pathway activity and type I/III collagen production. Our previous findings suggest that ELL-associated factor 2 (EAF2) may play a tumor suppressor and protective role in the development and progression of CRC by regulating signal transducer and activator of transcription 3 (STAT3)/TGF-β1 signaling pathway. However, the functional role and mechanism of VASH1-mediated TGF-β1 related pathway in CRC has not been elucidated.
AIM To investigate the expression of VASH1 in CRC and its correlation with the expression of EAF2. Furthermore, we studied the functional role and mechanism of VASH1 involved in the regulation and protection of EAF2 in CRC cells in vitro.
METHODS We collected colorectal adenocarcinoma and corresponding adjacent tissues to investigate the clinical expression of EAF2 protein and VASH1 protein in patients with advanced CRC. Following, we investigated the effect and mechanism of EAF2 and VASH1 on the invasion, migration and angiogenesis of CRC cells in vitro using plasmid transfection.
RESULTS Our findings indicated that EAF2 was down-regulated and VASH1 was up-regulated in advanced CRC tissue compared to normal colorectal tissue. Kaplan-Meier survival analysis showed that the higher EAF2 Level group and the lower VASH1 Level group had a higher survival rate. Overexpression of EAF2 might inhibit the activity of STAT3/TGF-β1 pathway by up-regulating the expression of VASH1, and then weaken the invasion, migration and angiogenesis of CRC cells.
CONCLUSION This study suggests that EAF2 and VASH1 may serve as new diagnostic and prognostic markers for CRC, and provide a clinical basis for exploring new biomarkers for CRC. This study complements the mechanism of EAF2 in CRC cells, enriches the role and mechanism of CRC cell-derived VASH1, and provides a new possible subtype of CRC as a therapeutic target of STAT3/TGF-β1 pathway.
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Affiliation(s)
- Ming-Liang Feng
- Department of Endoscopy, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
| | - Ming-Jun Sun
- Department of Endoscopy, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bo-Yang Xu
- Department of Endoscopy, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
| | - Meng-Yuan Liu
- Department of Endoscopy, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
| | - Hui-Jing Zhang
- Department of Endoscopy, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
| | - Can Wu
- Department of Endoscopy, The First Hospital Affiliated to China Medical University, Shenyang 110001, Liaoning Province, China
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