Inhibition of DKK-1 by WAY262611 Inhibits Osteosarcoma Metastasis DOI Open Access
Adit Tal,

Shimara Gunawardana-Zeigler,

Da Peng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

ABSTRACT Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood. Patients who present with metastatic disease at diagnosis or relapse have a very poor prognosis, and this has not changed over past four decades. The Wnt signaling pathway plays role regulating osteogenesis implicated OS pathogenesis. DKK-1 inhibits canonical pathway, causing inhibition of osteoblast differentiation disordered repair. Our lab previously demonstrated that monoclonal antibody against prevented mouse model. This study expands upon those findings by demonstrating similar results small molecule inhibitor DKK-1, WAY262611, both vitro vivo . WAY262611 was evaluated on osteosarcoma cell lines, including proliferation, caspase activation, cycle analysis, activation. We utilized our orthotopic implantation-amputation model metastasis to determine impact progression outgrowth disseminated cells. Differentiation status determined using single RNA sequencing. show here activates signaling, enhances nuclear localization transcriptional activity beta-catenin, slows proliferation lines. also induces osteoblastic an patient-derived xenograft , as well inhibiting metastasis. work credentials therapeutic target OS, allowing for manipulation providing preclinical justification development new biologics prevention

Language: Английский

Pre-metastatic niche: formation, characteristics and therapeutic implication DOI Creative Commons
Yuhang Wang,

Jiachi Jia,

Fuqi Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Sept. 25, 2024

Language: Английский

Citations

19
Effect of Extracellular Vesicles Derived From Tumor Cells on Immune Evasion DOI Creative Commons

Xixi Liu,

Kenneth K.W. To,

Qinsong Zeng

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

The crosstalk between immunity and cancer in the regulation of tumor growth is considered a hallmark cancer. Antitumor refers to innate adaptive immune responses that regulate development proliferation. Tumor evasion represents major hindrance effective anticancer treatment. Extracellular vesicles (EVs) are nano-sized lipid-bilayer-enclosed particles secreted extracellular space by all cell types. They critically involved numerous biological functions including intercellular communication. Tumor-derived (TEVs) can transport variety cargo modulate cells microenvironment (TME). This review provides latest update about how evade surveillance exploiting TEVs. First, biogenesis EVs cargo-sorting machinery discussed. Second, differentiation, activation, function via TEVs illustrated. Last but not least, novel antitumor strategies reverse escape summarized.

Language: Английский

Citations

0
CXCL2: a key player in the tumor microenvironment and inflammatory diseases DOI Creative Commons

Yuanhao Lv,

Chuin‐Shan Chen,

Miaomiao Han

et al.

Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 7, 2025

Language: Английский

Citations

0
Activin A from primary breast tumors generates a pre-metastatic niche by inducing pulmonary fibrosis DOI
Takuya Shirakihara, Akira Orimo

Translational Breast Cancer Research, Journal Year: 2024, Volume and Issue: 5, P. 24 - 24

Published: July 1, 2024

Language: Английский

Citations

1
Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies DOI Creative Commons
Jianlin Shen,

Yue Lai,

Yanjiao Wu

et al.

Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: 21(10), P. 880 - 897

Published: Oct. 30, 2024

Ubiquitination, a multifaceted post-translational modification, regulates protein function, degradation, and gene expression. The pivotal role of ubiquitination in the pathogenesis progression cancer, including colorectal, breast, liver is well-established. Osteosarcoma, an aggressive bone tumor predominantly affecting adolescents, also exhibits dysregulation system, encompassing both deubiquitination processes. This now recognized as key driver osteosarcoma development, progression, chemoresistance. review highlights recent progress elucidating how modulates behavior across signaling pathways. We then focus on mechanisms by which influences cell function. Finally, we discuss potential for targeting ubiquitin-proteasome system therapy. By unraveling impact physiology, aim to facilitate development novel strategies prognosis, staging, treatment, overcoming

Language: Английский

Citations

1
Metastasis-initiating osteosarcoma subpopulations establish paracrine interactions with both lung and tumor cells to create a metastatic niche DOI Open Access
James B. Reinecke, Amanda Saraf,

J. M. Hinckley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 10, 2024

ABSTRACT Osteosarcoma is an aggressive and deadly bone tumor, primarily afflicting children, adolescents, young adults. Poor outcomes for osteosarcoma patients are intricately linked with the development of lung metastasis. While metastasis responsible nearly all deaths caused by osteosarcoma, identification biologically defined, metastasis-targeting therapies remains elusive because underlying cellular molecular mechanisms that govern metastatic colonization circulating tumor cells to poorly understood. thousands released into circulation each day, very few can colonize lung. Herein, using a combination novel organotypic in vitro model, single-cell RNA sequencing, human xenograft, murine immunocompetent models, we find initiated subpopulation hypo-proliferative unique capacity sustain production promoting cytokines such as IL6 CXCL8 response lung-epithelial derived IL1α. Critically, genomic pharmacologic disruption IL1 signaling significantly reduces progression. Collectively, our study supports tumor-stromal interactions important metastasis, suggests competency driven, part, cell’s ability respond niche. Our findings support promising therapeutic approach disrupt

Language: Английский

Citations

0
The role of neutrophils in osteosarcoma: insights from laboratory to clinic DOI Creative Commons
Ming Xia, Yu Han,

Lihui Sun

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 8, 2024

Osteosarcoma, a highly aggressive malignant bone tumor, is significantly influenced by the intricate interactions within its tumor microenvironment (TME), particularly involving neutrophils. This review delineates multifaceted roles of neutrophils, including tumor-associated neutrophils (TANs) and neutrophil extracellular traps (NETs), in osteosarcoma’s pathogenesis. TANs exhibit both pro- anti-tumor phenotypes, modulating growth immune evasion, while NETs facilitate cell adhesion, migration, immunosuppression. Clinically, neutrophil-related markers such as neutrophil-to-lymphocyte ratio (NLR) predict patient outcomes, highlighting potential for neutrophil-targeted therapies. Unraveling these complex crucial developing novel treatment strategies that harness TME to improve osteosarcoma management.

Language: Английский

Citations

0
Significance of exosomes in osteosarcoma research: a systematic review and meta-analysis of a singular clinical investigation DOI Creative Commons
Xuehong Liu,

Jingyao Ye,

Wenlong Guo

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: Nov. 13, 2024

Osteosarcoma is the most prevalent among primary bone malignancies, and its standard intervention involves neoadjuvant chemotherapy - surgical adjuvant (MAP regimen) with adriamycin, cisplatin, high-dose methotrexate. Early-stage osteosarcoma can be effectively treated resection along or radiotherapy. However, as cancer progresses, efficacy of chemo- radiotherapy decreases, associated problems increase. The current understanding development, diagnosis, treatment does not meet clinical demands. More recently, there has been a significant increase in exosome-associated research, potentially opening up novel possibilities for research.

Language: Английский

Citations

0
Inhibition of DKK-1 by WAY262611 Inhibits Osteosarcoma Metastasis DOI Open Access
Adit Tal,

Shimara Gunawardana-Zeigler,

Da Peng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 11, 2024

ABSTRACT Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood. Patients who present with metastatic disease at diagnosis or relapse have a very poor prognosis, and this has not changed over past four decades. The Wnt signaling pathway plays role regulating osteogenesis implicated OS pathogenesis. DKK-1 inhibits canonical pathway, causing inhibition of osteoblast differentiation disordered repair. Our lab previously demonstrated that monoclonal antibody against prevented mouse model. This study expands upon those findings by demonstrating similar results small molecule inhibitor DKK-1, WAY262611, both vitro vivo . WAY262611 was evaluated on osteosarcoma cell lines, including proliferation, caspase activation, cycle analysis, activation. We utilized our orthotopic implantation-amputation model metastasis to determine impact progression outgrowth disseminated cells. Differentiation status determined using single RNA sequencing. show here activates signaling, enhances nuclear localization transcriptional activity beta-catenin, slows proliferation lines. also induces osteoblastic an patient-derived xenograft , as well inhibiting metastasis. work credentials therapeutic target OS, allowing for manipulation providing preclinical justification development new biologics prevention

Language: Английский

Citations

0