NF-κB signaling and integrin-β1 inhibition attenuates osteosarcoma metastasis via increased cell apoptosis

Li, Rui; Shi, Yanlong; Zhao, Shiwei; Shi, Tingting; Gui-chun, Zhang

doi:10.1016/j.ijbiomac.2018.11.003

Cited by 44 publications

(24 citation statements)

References 31 publications

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“…Several studies have shown inhibition of integrin or its downstream effectors to block many of the major hallmarks of cancer [ 137 – 139 ]. Additionally, selective knockdown of integrins significantly inhibits OS growth and lung metastasis, and an exogenous reintroduction of integrins can restore cell proliferation and lung metastasis in xenograft models of OS [ 140 ]. As pulmonary metastasis is the major cause of patient death in OS, these findings are especially promising and warrant future works.…”

Section: Ecm Components As Potential Therapeutic Targets In Osmentioning

confidence: 99%

The role of extracelluar matrix in osteosarcoma progression and metastasis

Cui

Dean

Hornicek

et al. 2020

J Exp Clin Cancer Res

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Osteosarcoma (OS) is the most common primary bone malignancy and responsible for considerable morbidity and mortality due to its high rates of pulmonary metastasis. Although neoadjuvant chemotherapy has improved 5-year survival rates for patients with localized OS from 20% to over 65%, outcomes for those with metastasis remain dismal. In addition, therapeutic regimens have not significantly improved patient outcomes over the past four decades, and metastases remains a primary cause of death and obstacle in curative therapy. These limitations in care have given rise to numerous works focused on mechanisms and novel targets of OS pathogenesis, including tumor niche factors. OS is notable for its hallmark production of rich extracellular matrix (ECM) of osteoid that goes beyond simple physiological growth support. The aberrant signaling and structural components of the ECM are rich promoters of OS development, and very recent works have shown the specific pathogenic phenotypes induced by these macromolecules. Here we summarize the current developments outlining how the ECM contributes to OS progression and metastasis with supporting mechanisms. We also illustrate the potential of tumorigenic ECM elements as prognostic biomarkers and therapeutic targets in the evolving clinical management of OS.

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Section: Ecm Components As Potential Therapeutic Targets In Osmentioning

confidence: 99%

The role of extracelluar matrix in osteosarcoma progression and metastasis

Cui

Dean

Hornicek

et al. 2020

J Exp Clin Cancer Res

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“…It revealed that only αvβ3 integrin expression in tumoral cells could predict benefit from cilengitide inhibition in a subset of patients with glioblastoma lacking MGMT promoter methylation. [60] Similarly, high levels of α5 or β1 integrin protein expression corre-sponded to worse survival in oral carcinoma, [61] triple-negative breast cancer, [62] pancreatic cancer, [63] osteosarcoma, [64] and colorectal cancer. [65] In the last period, data concerning integrin expressions and functions in nontumoral cells in the microenvironment of tumors have been increasingly reported.…”

Section: Integrins In the Hallmarks Of Cancermentioning

confidence: 99%

Biological Relevance of RGD‐Integrin Subtype‐Specific Ligands in Cancer

et al. 2020

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Integrins are heterodimeric transmembrane proteins able to connect cells with the micro‐environment. They represent a family of receptors involved in almost all the hallmarks of cancer. Integrins recognizing the Arg‐Gly‐Asp (RGD) peptide in their natural extracellular matrix ligands have been particularly investigated as tumoral therapeutic targets. In the last 30 years, intense research has been dedicated to designing specific RGD‐like ligands able to discriminate selectively the different RGD‐recognizing integrins. Chemists′ efforts have led to the proposition of modified peptide or peptidomimetic libraries to be used for tumor targeting and/or tumor imaging. Here we review, from the biological point of view, the rationale underlying the need to clearly delineate each RGD‐integrin subtype by selective tools. We describe the complex roles of RGD‐integrins (mainly the most studied αvβ3 and α5β1 integrins) in tumors, the steps towards selective ligands and the current usefulness of such ligands. Although the impact of integrins in cancer is well acknowledged, the biological characteristics of each integrin subtype in a specific tumor are far from being completely resolved. Selective ligands might help us to reconsider integrins as therapeutic targets in specific clinical settings.

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“…The transformation of normal cells into cancer cells is a complex process, in which integrins play a critical role by mediating cell-to-cell adhesion and their adhesion to the extracellular matrix [ 5 ]. Notably, higher levels of integrin expression enhance metastasis in different types of cancers [ 6 ], including osteosarcoma [ 7 , 8 , 9 ]. Some research has suggested that integrin may be a promising therapeutic target for osteosarcoma [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis

Tsai

Lai

Hsu

et al. 2021

IJMS

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Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvβ3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and β3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvβ3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvβ3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvβ3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.

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NF-κB signaling and integrin-β1 inhibition attenuates osteosarcoma metastasis via increased cell apoptosis

Cited by 44 publications

References 31 publications

The role of extracelluar matrix in osteosarcoma progression and metastasis

The role of extracelluar matrix in osteosarcoma progression and metastasis

Biological Relevance of RGD‐Integrin Subtype‐Specific Ligands in Cancer

CCL4 Stimulates Cell Migration in Human Osteosarcoma via the mir-3927-3p/Integrin αvβ3 Axis

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