A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells

Varès, Guillaume; Ahire, Vidhula; Sunada, Shigeaki; Kim, Eun Ho; Sai, Sei; Chevalier, François; Roméo, Paul-Henri; Yamamoto, Tadashi; Nakajima, Tetsuo; Saintigny, Yannick

doi:10.1016/j.radonc.2020.07.034

Cited by 16 publications

(22 citation statements)

References 68 publications

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“…Furthermore, ALDH-positive, but not ALDH-negative, cells showed an expression of the Krüppel-like factor 4 (KLF4) protein, which is one of the so-called Yamanaka factors of pluripotency. This may contribute significantly to the maintenance of a stem-like phenotype in ChS cells [54].…”

Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

“…The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K-AKT-mTOR) signaling pathway is involved in maintaining stem-like phenotypes. Rapamycin, an mTOR pharmacological inhibitor, significantly increased the level of suppressive miR-34 accompanied by the overexpression of Forkhead box O transcription factor 3 (FOXO3), which resulted in an inhibited proliferation of stem cells [54]. The mTOR inhibition also reduces the number of ALDH + cells and the loss of sphere formation ability in ChS in vitro [54].…”

Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

“…Rapamycin, an mTOR pharmacological inhibitor, significantly increased the level of suppressive miR-34 accompanied by the overexpression of Forkhead box O transcription factor 3 (FOXO3), which resulted in an inhibited proliferation of stem cells [54]. The mTOR inhibition also reduces the number of ALDH + cells and the loss of sphere formation ability in ChS in vitro [54]. Additionally, tumorsuppressive microRNA-34 (miR-34), well-known for the modulation of such target genes as Notch homolog 1 (NOTCH1), C-MYC, lemur tyrosine kinase 3 (LMTK3), and KLF4 [55], consequently can suppress stem-like characteristics in many types of cancer [56][57][58] and is suggested to influence stemness in ChS.…”

Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

“…Additionally, tumorsuppressive microRNA-34 (miR-34), well-known for the modulation of such target genes as Notch homolog 1 (NOTCH1), C-MYC, lemur tyrosine kinase 3 (LMTK3), and KLF4 [55], consequently can suppress stem-like characteristics in many types of cancer [56][57][58] and is suggested to influence stemness in ChS. Generally, miR-34 is downregulated in ChS cell lines, and its overexpression significantly reduced the invasive activity of ChS and the spheroid formation ability of ChS cells maintained in vitro [54].…”

Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

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Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

Zając

Król

Rutkowski

et al. 2021

Cancers

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Chondrosarcoma (ChS) is a primary malignant bone tumor. Due to its heterogeneity in clinical outcomes and resistance to chemo- and radiotherapies, there is a need to develop new potential therapies and molecular targets of drugs. Many genes and pathways are involved in in ChS progression. The most frequently mutated genes are isocitrate dehydrogenase ½ (IDH1/2), collagen type II alpha 1 chain (COL2A1), and TP53. Besides the point mutations in ChS, chromosomal aberrations, such as 12q13 (MDM2) amplification, the loss of 9p21 (CDKN21/p16/INK4A and INK4A-p14ARF), and several gene fusions, commonly occurring in sarcomas, have been found. ChS involves the hypermethylation of histone H3 and the decreased methylation of some transcription factors. In ChS progression, changes in the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K–AKT–mTOR) and hedgehog pathways are known to play a role in tumor growth and chondrocyte proliferation. Due to recent discoveries regarding the potential of immunotherapy in many cancers, in this review we summarize the current state of knowledge concerning cellular markers of ChS and tumor-associated immune cells. This review compares the latest discoveries in ChS biology from gene alterations to specific cellular markers, including advanced molecular pathways and tumor microenvironment, which can help in discovering new potential checkpoints in inhibitory therapy.

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Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

Section: Chondrosarcoma Stem Cellmentioning

confidence: 99%

See 2 more Smart Citations

Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

Zając

Król

Rutkowski

et al. 2021

Cancers

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“…[20][21][22][23][24] In another recent report, we demonstrated that carbon-ion beam irradiation combined with miR-34 mimic and/or rapamycin or miR-29b effectively eradicated high-grade chondrosarcoma CSCs and osteosarcoma cells via the mTOR-FOXO3 axis and the PTEN/AKT-SP1 pathway. 25,26 miR-200c, known as a tumor suppressor, is involved in inhibiting tumor growth and metastasis by suppressing the CSCs, this process is thought to be closely related to drug resistance and recurrence. [27][28][29][30][31][32][33][34][35] Thus, it is very important to develop a strategy to eliminate CSCs efficiently.…”

Section: Introductionmentioning

confidence: 99%

Carbon-Ion Beam Irradiation and the miR-200c Mimic Effectively Eradicate Pancreatic Cancer Stem Cells Under in vitro and in vivo Conditions

Sai¹,

Kim²,

Koom³

et al. 2021

OTT

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Purpose The study investigated the molecular mechanisms that killed pancreatic cancer cells, including cancer stem cells (CSCs), by carbon ion beam irradiation alone or in combination with miRNA-200c under in vitro and in vivo conditions. Methods Human pancreatic cancer (PC) cells, PANC1 and PK45, were treated with carbon-ion beam irradiation alone or in combination with microRNA-200c (miR-200c) mimic. Cell viability assay, colony and spheroid formation assay, quantitative real-time PCR analysis of apoptosis-, autophagy-, and angiogenesis-related gene expression, xenograft tumor control and histopathological analyses were performed. Results The cell viability assay showed that transfection of the miRNA-200c (10 nM) mimic into pancreatic CSC (CD44+/ESA+) and non-CSC (CD44-/ESA-) significantly suppressed proliferation of both types of cell populations described above. Combining carbon-ion beam irradiation with the miRNA-200c mimic significantly reduced the colony as well as spheroid formation abilities compared to that observed with the treatment of carbon-ion beam alone or X-ray irradiation combined with the miRNA-200c mimic. Moreover, the combination of carbon ion beam irradiation and miRNA-200c mimic increased the expression of apoptosis-related gene BAX, autophagy-related genes Beclin-1 and p62 , addition of gemcitabine (GEM) further enhanced the expression of these genes. In vivo data showed that carbon-ion beam irradiation in combination with the miRNA-200c mimic effectively suppressed xenograft tumor growth and significantly induced tumor necrosis and cavitation. Conclusion The combination of miRNA-200c mimic and carbon ion beam irradiation may be powerful radiotherapy that significantly kills pancreatic cancer cells containing CSCs and enhances the effect of carbon-ion beam irradiation compared to carbon-ion beam irradiation alone.

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The rationale for a carbon ion radiation therapy facility in Australia

Thwaites,

Prokopovich,

Garrett

et al. 2023

J of Medical Radiation Sci

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Australia has taken a collaborative nationally networked approach to achieve particle therapy capability. This supports the under‐construction proton therapy facility in Adelaide, other potential proton centres and an under‐evaluation proposal for a hybrid carbon ion and proton centre in western Sydney. A wide‐ranging overview is presented of the rationale for carbon ion radiation therapy, applying observations to the case for an Australian facility and to the clinical and research potential from such a national centre.

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A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells

Cited by 16 publications

References 68 publications

Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

Biological Heterogeneity of Chondrosarcoma: From (Epi) Genetics through Stemness and Deregulated Signaling to Immunophenotype

Carbon-Ion Beam Irradiation and the miR-200c Mimic Effectively Eradicate Pancreatic Cancer Stem Cells Under in vitro and in vivo Conditions

The rationale for a carbon ion radiation therapy facility in Australia

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