iScience
·
2023
·
IF 5.8
Xiao Qi,Zihao Li,Jinrui Zhang,Hongru Li,Guangxin Zhang,Meng Li,Baofeng Li,Yilin Fu,Mingjun Cai,Hongda Wang,Ti Tong,Jing Gao
CDCP1 is a transmembrane protein that is involved in a variety of important biological processes and upregulated in a variety of human solid malignancies; however, its spatial distribution and variation at the molecular level remain unclear. To solve this problem, we first analyzed its expression level and prognostic implications in lung cancer. Then, we used super-resolution microscopy to reveal the spatial organization of CDCP1 at different levels, and found that cancer cells generated more and larger CDCP1 clusters than normal cells. Furthermore, we found that CDCP1 can be integrated into larger and denser clusters as functional domains upon activation. Our findings elucidated the significant differences of CDCP1 clustering characteristics between cancer and normal cells, and revealed the relationship between its distribution and function, which will contribute to a comprehensive understanding of its oncogenic mechanism, and will be of great help for the development of CDCP1-targeted drugs for lung cancer.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
·
成像科学
✓ 已验证
DOI
PubMed
高影响因子
Journal for ImmunoTherapy of Cancer
·
2024
·Vol. 12
·期 10
·e009416
·
IF 10.3
Hua Huang,Yuwen Pan,Qiuwen Mai,Chunyu Zhang,Qiqiao Du,Yuandong Liao,Shuhang Qin,Yili Chen,Jiaming Huang,Jie Li,Tianyu Liu,Qiaojian Zou,Yijia Zhou,Li Yuan,Wei Wang,Yanchun Liang,Chao Yun Pan,Junxiu Liu,Shuzhong Yao
Background Cervical cancer remains a global health challenge. The identification of new immunotherapeutic targets may provide a promising platform for advancing cervical cancer treatment. Objective This study aims to investigate the role of CUB domain-containing protein 1 (CDCP1) in cervical cancer progression and evaluate its potential as a therapeutic target. Methods We performed comprehensive analyses using patient cohorts and preclinical models to examine the association between CDCP1 expression and cervical cancer prognosis. Then in immunodeficient and immunocompetent mouse models, we further investigated the impact of CDCP1 on the tumor immune microenvironment, focusing on its effects on tumor-infiltrating T cells, including cytotoxic T lymphocytes (CTLs) and regulatory T cells (Tregs). Mechanistic studies were performed to elucidate the pathways involved in CDCP1-mediated immune modulation, in particular its interaction with the T cell receptor CD6 and the activation of the JAK-STAT signaling pathway. Results Our results show that CDCP1 overexpression is associated with poor prognosis and T cell infliction in cervical cancer. Specifically, it affects the activity of CTLs and Tregs. Mechanistically, CDCP1 binds to CD6 and inhibits the JAK-STAT pathway of T cells. The study further demonstrates that targeting CDCP1 with the inhibitor 8-prenylnaringenin (8PN) effectively suppresses tumor growth in vivo and enhances antitumor immunity. Conclusions CDCP1 plays a critical role in cervical cancer progression by modulating the tumor immune microenvironment. Targeting CDCP1 offers a promising therapeutic strategy to improve the outcome of patients with cervical cancer.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
CLINICAL HEMORHEOLOGY AND MICROCIRCULATION
·
2022
·Vol. 80
·期 1
·25-35
·
IF 2.411
Zhao Meng,Zhu Yunkai,Zhang Yanhua,Yang Xupeng,Duan Yourong,Chen Yaqing,Sun Ying
BACKGROUND:Molecular targeted contrast-enhanced ultrasound (CEUS) imaging is a potential imaging strategy to improve the diagnostic accuracy of conventional ultrasound (US) imaging. US contrast agents are usually micrometer-sized and non-target gas bubbles while nano-sized and targeted agents containing phase-shift materials absorb more attractions for their size and the liquid core and excellent molecular imaging effect. METHODS:PLGA12k-mPEG2k-NH2, DSPE-mPEG2k and perfluorohexan (PFH) were used to construct a new targeted ultrasound contrast agent with CUB domain-containing protein 1 (CDCP1) receptor for the detection and diagnosis of prostate cancer. The potential of tumor-targeted nanoparticles (CDCP1-targeted perfluorohexan-loaded phase-transitional nanoparticles, anti-CDCP1 NPs) as contrast agents for ultrasound (US) imaging was assessed in vitro. Moreover, studies on the cytotoxicity and the targeting ability of anti-CDCP1 NPs assisted by US were carried out. RESULTS:The results showed that anti-CDCP1 NPs had low cytotoxicity, and with the increasing of polymer concentration in anti-CDCP1 NPs, the CEUS imaging of agent gradually enhanced, and enhanced imaging associated with the length of observing time. Furthermore, it was testified that anti-CDCP1 assisted the agent to target cells expressing CDCP1, which demonstrated the active targeting of anti-CDCP1 NPs in vitro. CONCLUSION:All in all, the feasibility of using targeted anti-CDCP1 NPs to enhance ultrasound imaging has been demonstrated in vitro, which laid a solid foundation for molecular US imaging in vivo, and anti-CDCP1 NPs might have a great clinical application prospect.
研究领域:
医学成像
·
纳米技术
·
肿瘤学
·
超声技术
✓ 已验证
DOI
PubMed
高影响因子
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