Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation

Xiao, Yansen; Ma, Cong; Li, Jiatao; He, Dasa; Wu, Qiuyao; Tian, Pu; Wang, Yuan; Yang, Shenghong; Liang, Chenxi; Liang, Yajun; Wen, Jili; Liu, Yingjie; Luo, Wenqian; Lv, Xianzhe; He, Yunfei; Cheng, Dongdong; Zhou, Tianhao; Zhao, Wenjing; Zhang, Peiyuan; Zhang, Xue; Xiao, Yichuan; Qian, Youcun; Wang, Hongxia; Gao, Qiang; Yang, Qingcheng; Yang, Qifeng; Hu, Guohong

doi:10.1016/j.ccell.2020.12.012

Cited by 372 publications

(306 citation statements)

References 77 publications

(102 reference statements)

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“…The formation of NETs may be partly due to the hypoxic environment in which growing solid tumors are generated concomitant with the higher expression of HIF-1α [ 20 , 21 ]. Moreover, secreted cytokines [ 18 , 48 , 58 , 64 , 67 ], proteases [ 68 ] and even exosomes [ 57 ] may also contribute to NET formation ( Figure 1 ). Depletion of IL-8, G-CSF, GROα or GROβ derived from ovarian cancer cells can incompletely reduce NET formation and neutrophil chemotaxis, suggesting that these cytokines cooperate with each other to optimally stimulate neutrophil mobilization and NET formation [ 65 ].…”

Section: Net Formationmentioning

confidence: 99%

“…Xiao et al found that the tumor-secreted protease cathepsin C (CTSC) enzymatically activates neutrophil membrane-bound proteinase 3 (PR3) to upregulate IL-6 and CCL3 for neutrophil recruitment. In addition, the CTSC–PR3–IL-1β axis induces the formation of NETs which support the metastasis of cancer cells in the lungs [ 68 ]. Furthermore, tumor-derived exosomes have been closely linked to NET formation.…”

Section: Net Formationmentioning

confidence: 99%

“…A recent study reported further mechanisms of interaction between NETs and tumor cells in lung premetastatic niches of breast cancer. Xiao et al found that the tumor-secreted protease cathepsin C (CTSC) promotes breast-to-lung metastasis by regulating the recruitment of neutrophils and formation of NETs [ 68 ].…”

Section: Nets Promote Tumor Metastasismentioning

confidence: 99%

“…Considering the significant prometastatic functions of NETs, targeting NETs can be a promising approach against tumor metastasis. Animal studies have shown inhibition of tumor metastasis by blocking NET formation with the application of small molecule drugs such as DNase [ 21 , 58 , 62 , 66 ], CTSC inhibitors [ 68 ], PAD4 inhibitors [ 19 , 64 , 109 , 110 ] and NE inhibitors [ 62 , 66 ]. DNase I treatment suppressed the development of gross metastases and the growth of established liver micrometastases in metastatic colorectal cancer animal models [ 21 ].…”

Section: The Clinical Significance Of Netsmentioning

confidence: 99%

“…AZD7986 is a second-generation CTSC inhibitor and a therapeutic candidate for neutrophil-driven inflammatory diseases, such as chronic obstructive pulmonary disease [ 111 , 112 ]. Interestingly, targeting CTSC with the compound AZD7986 effectively suppressed circulating pulmonary NETs and alleviated lung metastasis of breast cancer in a mouse model, but there was no effect on primary tumor growth [ 68 ]. The PAD4 inhibitor Cl-amidine significantly reduced NET formation, but the number of breast cancer cells that extravasated into the lung tissue was not altered [ 64 ].…”

Section: The Clinical Significance Of Netsmentioning

confidence: 99%

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Neutrophil Extracellular Traps in Tumor Metastasis: Pathological Functions and Clinical Applications

Chen

Zhang

et al. 2021

Cancers

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Neutrophil extracellular trap (NET) formation is an ability of neutrophils to capture and kill pathogens by releasing chromatin scaffolds, along with associated cytotoxic enzymes and proteases, into the extracellular space. NETs are usually stimulated by pathogenic microorganisms and their products, surgical pressure or hypoxia. Interestingly, a number of recent studies suggest that tumor cells can induce NET formation, which in turn confers tumor cell malignancy. Notably, emerging studies indicate that NETs are involved in enhancing local invasion, increasing vascular permeability and facilitating immune escape and colonization, thus promoting tumor metastasis. In this article, we review the pivotal roles of NETs in the tumor metastasis cascade. We also recapitulate the potential of NETs as a cancer prognostic biomarker and therapeutic target.

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Section: Net Formationmentioning

confidence: 99%

Section: Net Formationmentioning

confidence: 99%

Section: Nets Promote Tumor Metastasismentioning

confidence: 99%

Section: The Clinical Significance Of Netsmentioning

confidence: 99%

Section: The Clinical Significance Of Netsmentioning

confidence: 99%

See 3 more Smart Citations

Neutrophil Extracellular Traps in Tumor Metastasis: Pathological Functions and Clinical Applications

Chen

Zhang

et al. 2021

Cancers

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Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity

Gerashchenko,

Frolova,

Patysheva

et al. 2024

Advanced Biology

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Breast cancer (BC) is one of the most common malignancies in women worldwide. Numerous studies in immuno‐oncology and successful trials of immunotherapy have demonstrated the causal role of the immune system in cancer pathogenesis. The interaction between the tumor and the immune system is known to have a dual nature. Despite cytotoxic lymphocyte activity against transformed cells, a tumor can escape immune surveillance and leverage chronic inflammation to maintain its own development. Research on antitumor immunity primarily focuses on the role of the tumor microenvironment, whereas the systemic immune response beyond the tumor site is described less thoroughly. Here, a comprehensive review of the formation of the immune profile in breast cancer patients is offered. The interplay between systemic and local immune reactions as self‐sustaining mechanism of tumor progression is described and the functional activity of the main cell populations related to innate and adaptive immunity is discussed. Additionally, the interaction between different functional levels of the immune system and their contribution to the development of the pro‐ or anti‐tumor immune response in BC is highlighted. The presented data can potentially inform the development of new immunotherapy strategies in the treatment of patients with BC.

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Versatile Red Blood Cells for Triple‐Negative Breast Cancer Treatment via Stepwise Photoactivations

Cheng

Chen

Qian

et al. 2022

Adv Healthcare Materials

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Phototherapies have many advantages for triple-negative breast cancer (TNBC) treatment. However, their effects are often limited by short blood circulation time, poor tumor selectivity and weak penetration of phototherapeutic agents, and tumor hypoxia. For overcoming these limitations, a versatile biomimetic system is developed based on red blood cells (RBCs). Photothermal agent new indocyanine green (IR820) is conjugated with the cell/tissue-penetrating TAT peptide and further efficiently encapsulated into the intact RBCs by crossing cell membranes to realize the long blood circulation. Meanwhile, cyclic RGD peptide (cRGD) is linked to the surfaces of RBCs through phospholipid insertion to obtain tumor vessel-targeting ability. Photosensitizer temoporfin (mTHPC) is next loaded into the membranes of RBCs by spontaneous transferring. The acquired biomimetic system (cRGD-RBC@mTHPC/TAT-IR820) exhibits potent photodynamic performance upon 652 nm laser irradiation with the facilitation of oxyhemoglobin, which could not only trigger TAT-IR820 release but also destroy tumor vessels. TAT-IR820 penetrates deeply into tumor tissue via the mediation of TAT peptide, exerting greatly promoted photothermal ablation against TNBC upon 808 nm laser irradiation. In situ generated tumor antigens further induce robust immune responses to suppress TNBC recurrence and metastasis. In summary, this study provides a versatile biomimetic system for comprehensive TNBC treatment via stepwise photodynamic and photothermal activations.

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Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation

Cited by 372 publications

References 77 publications

Neutrophil Extracellular Traps in Tumor Metastasis: Pathological Functions and Clinical Applications

Neutrophil Extracellular Traps in Tumor Metastasis: Pathological Functions and Clinical Applications

Breast Cancer Immune Landscape: Interplay Between Systemic and Local Immunity

Versatile Red Blood Cells for Triple‐Negative Breast Cancer Treatment via Stepwise Photoactivations

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