Nebulized Therapy of Early Orthotopic Lung Cancer by Iron-Based Nanoparticles: Macrophage-Regulated Ferroptosis of Cancer Stem Cells DOI

Qishuai Feng,

Wenming Fang,

Yuedong Guo

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(44), P. 24153 - 24165

Published: Oct. 28, 2023

Cancer stem cells (CSCs) within protumorigenic microlesions are a critical driver in the initiation and progression of early stage lung cancer, where immune provide an immunosuppressive niche to strengthen CSC stemness. As mutual interactions between CSCs increasingly recognized, regulating identify effectively eliminate has recently become one most attractive therapeutic options, especially for abundant tumor-associated macrophages (TAMs). Herein, we developed nebulized nanocatalytic medicine strategy which iron-based nanoparticle-regulated TAMs target niches trigger ferroptosis cancer. Briefly, nanoparticles can accumulate cancer (minimum 122 μm diameter) through dextran-mediated TAM targeting by nebulization administration, as result, nanoparticle-internalized play predominant role iron factory elevating level surrounding destroying redox equilibrium downregulating glucose-6-phosphate metabolite following their lysosomal degradation metabolism. The altered microenvironment results enhanced sensitivity due high expression CD44 receptor mediating endocytosis. In orthotopic mouse model significantly suppressed ferroptosis-induced stemness reduction administration. This work presents modulation communications CSCs, is expected be general approach primary micrometastatic

Language: Английский

Tumor-associated macrophages: an accomplice in solid tumor progression DOI Creative Commons
Yibing Chen,

Yucen Song,

Wei Du

et al.

Journal of Biomedical Science, Journal Year: 2019, Volume and Issue: 26(1)

Published: Oct. 19, 2019

In many solid tumor types, tumor-associated macrophages (TAMs) are important components of the microenvironment (TME). Moreover, TAMs infiltration is strongly associated with poor survival in patients. this review, we describe origins and their polarization state dictated by TME. We also specifically focus on role promoting growth, enhancing cancer cells resistance to chemotherapy radiotherapy, angiogenesis, inducing migration invasion metastasis, activating immunosuppression. addition, discuss can be used as therapeutic targets clinics. The strategies include clearing inhibiting activation TAMs, macrophage phagocytic activity, limiting monocyte recruitment other targeted therapies.

Language: Английский

Citations

890
Cancer stem cell–immune cell crosstalk in tumour progression DOI
Defne Bayık, Justin D. Lathia

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(8), P. 526 - 536

Published: June 8, 2021

Language: Английский

Citations

386
Wnt Signaling in Ovarian Cancer Stemness, EMT, and Therapy Resistance DOI Open Access

Miriam Teeuwssen,

Riccardo Fodde

Journal of Clinical Medicine, Journal Year: 2019, Volume and Issue: 8(10), P. 1658 - 1658

Published: Oct. 11, 2019

Ovarian cancers represent the deadliest among gynecologic malignancies and are characterized by a hierarchical structure with cancer stem cells (CSCs) endowed self-renewal capacity to differentiate. The Wnt/β-catenin signaling pathway, known regulate stemness in broad spectrum of cell niches including ovary, is thought play an important role ovarian cancer. Importantly, Wnt activity was shown correlate grade, epithelial mesenchymal transition, chemotherapy resistance, poor prognosis This review will discuss current knowledge stemness, transition (EMT), therapy resistance. In addition, alleged exosomes paracrine activation pre-metastatic niche formation be reviewed. Finally, novel potential treatment options based on inhibition highlighted.

Language: Английский

Citations

183
Cancer Stemness Meets Immunity: From Mechanism to Therapy DOI Creative Commons
Peiwen Chen, Wen‐Hao Hsu, Jincheng Han

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 34(1), P. 108597 - 108597

Published: Jan. 1, 2021

Cancer stem cells (CSCs) are self-renewing that facilitate tumor initiation, promote metastasis, and enhance cancer therapy resistance. Transcriptomic analyses across many types have revealed a prominent association between stemness immune signatures, potentially implying biological interaction such hallmark features of cancer. Emerging experimental evidence has substantiated the influence CSCs on cells, including tumor-associated macrophages, myeloid-derived suppressor T in microenvironment and, reciprocally, importance sustaining CSC its survival niche. This review covers cellular molecular mechanisms underlying symbiotic interactions how heterotypic signaling maintains tumor-promoting ecosystem informs therapeutic strategies intercepting this co-dependency.

Language: Английский

Citations

183
Wnt/β-catenin signalling in ovarian cancer: Insights into its hyperactivation and function in tumorigenesis DOI Creative Commons
Vu H. Nguyen,

Rebecca Hough,

Stefanie Bernaudo

et al.

Journal of Ovarian Research, Journal Year: 2019, Volume and Issue: 12(1)

Published: Dec. 1, 2019

Abstract Epithelial ovarian cancer (EOC) is the deadliest female malignancy. The Wnt/β-catenin pathway plays critical roles in regulating embryonic development and physiological processes. This tightly regulated to ensure its proper activity. In absence of Wnt ligands, β-catenin degraded by a destruction complex. When stimulated ligand, dissociates from complex translocates into nucleus where it interacts with TCF/LEF transcription factors regulate target gene expression. Aberrant activation this pathway, which leads hyperactivity β-catenin, has been reported cancer. Specifically, mutations CTNNB1 , AXIN, or APC, have observed endometrioid mucinous subtypes EOC. addition, upregulation abnormal receptors intracellular mediators, disruption complex, inhibition association β-catenin/E-cadherin on cell membrane, aberrant promotion β-catenin/TCF transcriptional activity, all EOC, especially high grade serous subtype. Furthermore, several non-coding RNAs shown EOC development, part, through modulation signalling. promote stem self-renewal, metastasis, chemoresistance Emerging evidence also suggests that induces tumor angiogenesis immune evasion. Taken together, these studies demonstrate strong candidate for targeted therapies.

Language: Английский

Citations

165
Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers DOI Open Access

Alicia Cristina Peña-Romero,

Esteban Orenes‐Piñero

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1681 - 1681

Published: March 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Language: Английский

Citations

149
Wnt signaling pathway in cancer immunotherapy DOI
Yang Zhou, Xu Jiang,

Haichang Luo

et al.

Cancer Letters, Journal Year: 2021, Volume and Issue: 525, P. 84 - 96

Published: Nov. 3, 2021

Language: Английский

Citations

138
Targeting Breast Cancer Stem Cells DOI Creative Commons
Lu Zhang, Wen‐Ming Chen, Suling Liu

et al.

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(2), P. 552 - 570

Published: Jan. 1, 2023

The potential roles of breast cancer stem cells (BCSCs) in tumor initiation and recurrence have been recognized for many decades.Due to their strong capacity self-renewal differentiation, BCSCs are the major reasons poor clinical outcomes low therapeutic response.Several hypotheses on origin proposed, including critical gene mutations cells, dedifferentiation somatic cell plasticity remodeling by epithelial-mesenchymal transition (EMT) microenvironment.Moreover, microenvironment, cellular components cytokines, modulates resistance BCSCs.Small molecules, antibodies, chimeric antigen receptor (CAR)-T targeting developed, applications combination with conventional therapies undergoing trials.In this review, we focus features BCSCs, emphasize factors environment that regulate stemness discuss BCSC-targeting therapies.

Language: Английский

Citations

112
WNT signaling and cancer stemness DOI Creative Commons

Masuko Katoh,

Masaru Katoh

Essays in Biochemistry, Journal Year: 2022, Volume and Issue: 66(4), P. 319 - 331

Published: July 15, 2022

Abstract Cancer stemness, defined as the self-renewal and tumor-initiation potential of cancer stem cells (CSCs), is a biology property featuring activation CSC signaling networks. Canonical WNT through Frizzled LRP5/6 receptors transmitted to β-catenin-TCF/LEF-dependent transcription machinery up-regulate MYC, CCND1, LGR5, SNAI1, IFNG, CCL28, CD274 (PD-L1) other target genes. causes expansion rapidly cycling CSCs modulates both immune surveillance tolerance. In contrast, noncanonical or ROR1/2 phospholipase C, Rac1 RhoA control transcriptional outputs mediated by NFAT, AP-1 YAP-TEAD, respectively. Noncanonical supports maintenance slowly cycling, quiescent dormant promotes epithelial–mesenchymal transition via crosstalk with TGFβ (transforming growth factor-β) cascades, while network induces evasion. The orchestrates functions cancer-associated fibroblasts, endothelial in tumor microenvironment fine-tunes stemness human cancers, such breast, colorectal, gastric lung cancers. Here, WNT-related features, including proliferation/dormancy plasticity, plasticity immune-landscape will be discussed. Porcupine inhibitors, β-catenin protein–protein interaction proteolysis targeting chimeras, ROR1 inhibitors ROR1-targeted biologics are investigational drugs cascades. Mechanisms regulated promising targets for therapeutic intervention; however, further understanding context-dependent reprogramming trajectories might necessary optimize clinical benefits WNT-targeted monotherapy applied combination therapy patients cancer.

Language: Английский

Citations

95
Molecular, cellular and systemic aspects of epithelial ovarian cancer and its tumor microenvironment DOI Creative Commons
Esther Schoutrop, Lidia Moyano‐Galceran, Stéphanie Lheureux

et al.

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 207 - 223

Published: April 5, 2022

Ovarian cancer encompasses a heterogeneous group of malignancies that involve the ovaries, fallopian tubes and peritoneal cavity. Despite major advances made within field cancer, majority patients with ovarian are still being diagnosed at an advanced stage disease due to lack effective screening tools. The overall survival these has, therefore, not substantially improved over past decades. Most undergo debulking surgery treatment chemotherapy, but often micrometastases remain acquire resistance therapy, eventually leading recurrence. Here, we summarize current knowledge in epithelial development metastatic progression. For most common subtypes, focus further on properties functions immunosuppressive tumor microenvironment, including extracellular matrix. Current future modalities discussed finally provide overview different experimental models used develop novel therapies.

Language: Английский

Citations

93