Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma DOI Creative Commons

Zhen Pan,

Xiaojuan Wei, Shi-jie Li

et al.

Oncogenesis, Journal Year: 2022, Volume and Issue: 11(1)

Published: April 13, 2022

Alginate oligosaccharide (AOS) has the function to inhibit tumor progression and sulfated modification can enhance antitumor activity. To date, mechanism of AOS (AOS-SO4) in tumors remain largely elusive. We prepared by enzymatic degradation alginate, collected AOS-SO4 sulfating following canonical procedure. Using these materials, vitro assays showed that both elicited effects osteosarcoma cells. Sulfated significantly enhanced In addition, had obvious on cell cycle arrest, apoptosis, autophagy induction vivo. Mechanistically, we observed treatment triggered proapoptotic inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, found KSR1 interacted with MEK1 functioned as a positive regulator protein High expression was associated poor survival patients. Together, results suggest better effect signaling, which is KSR1-dependent; thus, be new potential therapeutic candidate for osteosarcoma.

Language: Английский

Single-Cell Transcriptomics Reveals the Complexity of the Tumor Microenvironment of Treatment-Naive Osteosarcoma DOI Creative Commons
Yun Liu, Wenyu Feng, Yan Dai

et al.

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: July 21, 2021

Osteosarcoma (OS), which occurs most commonly in adolescents, is associated with a high degree of malignancy and poor prognosis. In order to develop an accurate treatment for OS, deeper understanding its complex tumor microenvironment (TME) required. the present study, tissues were isolated from six patients then subjected single-cell RNA sequencing (scRNA-seq) using 10× Genomics platform. Multiplex immunofluorescence staining was subsequently used validate subsets identified by scRNA-seq. ScRNA-seq OS performed prior neoadjuvant chemotherapy, data obtained on 29,278 cells. A total nine major cell types identified, transcriptional map revealed. Identified osteoblastic cells divided into five subsets, those significant prognostic correlation determined deconvolution algorithm. Thereby, different transcription patterns cellular subtypes reported, key factors survival prognosis identified. Furthermore, regulation osteolysis via receptor activator nuclear factor kappa-B ligand role regulating angiogenesis through vascular endothelial growth factor-A C3_TXNIP+ macrophages C5_IFIT1+ found regulate regulatory T participate CD8+ exhaustion, illustrating possibility immunotherapy that could target macrophages. Our findings here show C1_osteoblastic promote angiogenesis, this addition, depletion important feature OS. More importantly, study provided valuable resource in-depth heterogeneity TME.

Language: Английский

Citations

117
A novel signature to guide osteosarcoma prognosis and immune microenvironment: Cuproptosis-related lncRNA DOI Creative Commons
Mingyi Yang,

Haishi Zheng,

Ke Xu

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 29, 2022

Objective Osteosarcoma (OS) is a common bone malignancy with poor prognosis. We aimed to investigate the relationship between cuproptosis-related lncRNAs (CRLncs) and survival outcomes of patients OS. Methods Transcriptome clinical data 86 OS were downloaded from The Cancer Genome Atlas (TCGA). GSE16088 dataset was Gene Expression Omnibus (GEO) database. 10 genes (CRGs) obtained recently published article on cuproptosis in Science . Combined analysis transcriptome identified differentially expressed CRGs related Next, pathway enrichment performed. Co-expression CRLncs Univariate COX regression least absolute shrinkage selection operator (LASSO) used construct risk prognostic model CRLncs. samples divided evenly into training test groups verify accuracy model. Risk curve, survival, receiver operating characteristic (ROC) independent analyses principal component (PCA) t-distributed stochastic neighbor embedding (t-SNE) Single-sample gene set (ssGSEA) explore correlation models immune microenvironment. Drug sensitivity drugs potential efficacy Real-time quantitative PCR, Western blotting, immunohistochemistry verified expression PCR Results Six that can guide prognosis microenvironment obtained, including three high-risk (AL645608.6, AL591767.1, UNC5B-AS1) low-risk (CARD8-AS1, AC098487.1, AC005041.3). Immune cells such as B cells, macrophages, T-helper type 2 (Th2) regulatory T (Treg), functions APC co-inhibition, checkpoint, T-cell co-inhibition significantly downregulated groups. In addition, we four for OS: AUY922, bortezomib, lenalidomide, Z.LLNle.CHO. LIPT1, DLAT, FDX1 at both mRNA protein levels elevated cell lines compared normal osteoblast hFOB1.19. level AL591767.1 decreased OS, AL645608.6, CARD8-AS1, AC005041.3, UNC5B-AS1 upregulated Conclusion may have curative effect this study provide theoretical basis research decision-making.

Language: Английский

Citations

86
Injectable self-healing cellulose hydrogel based on host-guest interactions and acylhydrazone bonds for sustained cancer therapy DOI
Xueyu Jiang, Fanwei Zeng, Xuefeng Yang

et al.

Acta Biomaterialia, Journal Year: 2022, Volume and Issue: 141, P. 102 - 113

Published: Jan. 3, 2022

Language: Английский

Citations

73
Targeted therapy for osteosarcoma: a review DOI
Shizhe Li, He Zhang, Jinxin Liu

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2023, Volume and Issue: 149(9), P. 6785 - 6797

Published: Feb. 18, 2023

Language: Английский

Citations

47
Advances on immunotherapy for osteosarcoma DOI Creative Commons
Shengnan Yu, Xudong Yao

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Sept. 9, 2024

Language: Английский

Citations

38
Bioactive hydrogel formulations for regeneration of pathological bone defects DOI
Zuhao Li, Kaixuan Ren, Jiajia Chen

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 380, P. 686 - 714

Published: Feb. 17, 2025

Language: Английский

Citations

3
Emerging role of exosomes as biomarkers in cancer treatment and diagnosis DOI

Niloofar Asadi Hanjani,

Nazanin Esmaelizad, Saba Zanganeh

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2021, Volume and Issue: 169, P. 103565 - 103565

Published: Dec. 3, 2021

Language: Английский

Citations

84
MerTK-mediated efferocytosis promotes immune tolerance and tumor progression in osteosarcoma through enhancing M2 polarization and PD-L1 expression DOI Creative Commons

Jinti Lin,

Ankai Xu,

Jiakang Jin

et al.

OncoImmunology, Journal Year: 2022, Volume and Issue: 11(1)

Published: Jan. 12, 2022

The poor progress of immunotherapy on osteosarcoma patients requires deeper delineation immune tolerance mechanisms in the microenvironment and a new therapeutic strategy. Clearance apoptotic cells by phagocytes, process termed "efferocytosis," is ubiquitous tumors mediates suppression innate inflammatory response. Considering massive infiltrated macrophages osteosarcoma, efferocytosis probably serves as potential target, but rarely studied osteosarcoma. Here, we verified M2 polarization PD-L1 expression following efferocytosis. Pharmacological inhibition genetic knockdown were used to explore underlying pathway. Moreover, tumor progression landscape evaluated model. Our study indicated that promoted macrophages. Ëfferocytosis was mediated MerTK receptor regulated phenotypes through p38/STAT3 By establishing murine model, emphasized suppressed growth enhanced T cell cytotoxic function increasing infiltration CD8+ decreasing their exhaustion. findings demonstrate MerTK-mediated promotes enhancing PD-L1-induced tolerance, which

Language: Английский

Citations

58
Current Status and Prospects of Targeted Therapy for Osteosarcoma DOI Creative Commons
Zunguo Hu,

Shuang Wen,

Zijun Huo

et al.

Cells, Journal Year: 2022, Volume and Issue: 11(21), P. 3507 - 3507

Published: Nov. 5, 2022

Osteosarcoma (OS) is a highly malignant tumor occurring in bone tissue with high propensity to metastasize, and its underlying mechanisms remain largely elusive. The OS prognosis poor, improving the survival of patients remains challenge. Current treatment methods such as surgical approaches, chemotherapeutic drugs, immunotherapeutic drugs ineffective. As research progresses, targeted therapy gradually becoming irreplaceable. In this review, several modalities for osteosarcoma, surgery, chemotherapy, immunotherapy, are briefly described, followed by discussion therapy, important targets, new technologies osteosarcoma treatment.

Language: Английский

Citations

55
Tumor-associated macrophages induce inflammation and drug resistance in a mechanically tunable engineered model of osteosarcoma DOI Creative Commons

Letitia K. Chim,

Isabelle L. Williams, Caleb J. Bashor

et al.

Biomaterials, Journal Year: 2023, Volume and Issue: 296, P. 122076 - 122076

Published: March 7, 2023

Language: Английский

Citations

23