Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma

Camille Jubelin , Javier Muñoz-Garcia , Denis Cochonneau , Emilie Moranton , Marie-Françoise Heymann , Dominique Heymann

Cancer Drug Resistance ›› 2022, Vol. 5 ›› Issue (1) : 184 -98.

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Cancer Drug Resistance ›› 2022, Vol. 5 ›› Issue (1) :184 -98. DOI: 10.20517/cdr.2021.130
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Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma

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Abstract

Sarcomas are a large family of cancers originating in the mesenchyme. Composed of more than 100 histological subtypes, soft tissue and bone sarcomas remain clinically challenging, particularly in children and adolescents in whom sarcomas are the second most common malignant entities. Osteosarcoma is the main primary bone tumor in adolescents and young adults and is characterized by a high propensity to induce distant metastatic foci and become multi-drug resistant. The innate and acquired resistance of osteosarcoma can be explained by high histological heterogeneity and genetic/molecular diversity. In the last decade, the notion of cancer stem-like cells (CSCs) has emerged. This subset of cancer cells has been linked to drug resistance properties, recurrence of the disease, and therapeutic failure. Although CSCs remain controversial, many elements are in favor of them playing a role in the development of the drug resistance profile. The present review gives a brief overview of the most recent biological evidence of the presence of CSCs in osteosarcomas and their role in the drug resistance profile of these rare oncological entities. Their use as promising therapeutic targets is discussed.

Keywords

Cancer stem cells / bone sarcoma / soft tissue sarcoma / drug resistance / tumor microenvironment / recurrent disease / residual disease

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Camille Jubelin, Javier Muñoz-Garcia, Denis Cochonneau, Emilie Moranton, Marie-Françoise Heymann, Dominique Heymann. Biological evidence of cancer stem-like cells and recurrent disease in osteosarcoma. Cancer Drug Resistance, 2022, 5(1): 184-98 DOI:10.20517/cdr.2021.130

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References

[1]

Grünewald TG,Avnet S.Sarcoma treatment in the era of molecular medicine.EMBO Mol Med2020;12:e11131 PMCID:PMC7645378

[2]

Brown HK,Gouin F,Heymann D.Biology of bone sarcomas and new therapeutic developments.Calcif Tissue Int2018;102:174-95 PMCID:PMC5805807

[3]

Baumhoer D,Cates JMM. Osteosarcoma. WHO Classification of Tumours Editorial board. Soft tissue and bone tumours. Lyon (France): International Agency for Research on Cancer; 2020. p. 403-9.

[4]

Flanagan AM,O’Donnel PG. Secondary osteosarcoma. WHO Classification of Tumours Editorial board. Soft tissue and bone tumours. Lyon (France): International Agency for Research on Cancer; 2020. p. 419-21.

[5]

Gill J.Advancing therapy for osteosarcoma.Nat Rev Clin Oncol2021;18:609-24

[6]

Strauss SJ.Current questions in bone sarcomas.Curr Opin Oncol2018;30:252-9

[7]

Sarcoma Network Working Group. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.Ann Oncol2012;23 Suppl 7:vii100-9

[8]

Kovac M,Ribi S.Exome sequencing of osteosarcoma reveals mutation signatures reminiscent of BRCA deficiency.Nat Commun2015;6:8940 PMCID:PMC4686819

[9]

Behjati S,Haase K.Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma.Nat Commun2017;8:15936 PMCID:PMC5490007

[10]

Wu SP,Bu F.DNA methylation-based classifier for accurate molecular diagnosis of bone sarcomas.JCO Precis Oncol2017;2017 PMCID:PMC5772901

[11]

Morrow JJ,Funnell APW.Positively selected enhancer elements endow osteosarcoma cells with metastatic competence.Nat Med2018;24:176-85 PMCID:PMC5803371

[12]

Asano N,Yamashita S.Epigenetic reprogramming underlies efficacy of DNA demethylation therapy in osteosarcomas.Sci Rep2019;9:20360 PMCID:PMC6937291

[13]

Brown HK,Cartron PF,Heymann MF.Characterization of circulating tumor cells as a reflection of the tumor heterogeneity: myth or reality?.Drug Discov Today2019;24:763-72

[14]

Tellez-Gabriel M,Heymann D.Circulating tumor cells as a tool for assessing tumor heterogeneity.Theranostics2019;9:4580-94 PMCID:PMC6643448

[15]

Vallette FM,Lézot F.Dormant, quiescent, tolerant and persister cells: four synonyms for the same target in cancer.Biochem Pharmacol2019;162:169-76

[16]

Nassar D.Cancer stem cells: basic concepts and therapeutic implications.Annu Rev Pathol2016;11:47-76

[17]

Walcher L,Suo H.Cancer stem cells-origins and biomarkers: perspectives for targeted personalized therapies.Front Immunol2020;11:1280 PMCID:PMC7426526

[18]

Clarke MF.Clinical and therapeutic implications of cancer stem cells.N Engl J Med2019;380:2237-45

[19]

Halldorsson A,Montgomery S.Lung metastasis 21 years after initial diagnosis of osteosarcoma: a case report.J Med Case Rep2009;3:9298 PMCID:PMC2803821

[20]

Perrot P,Bouffaut AL.Safety concern between autologous fat graft, mesenchymal stem cell and osteosarcoma recurrence.PLoS One2010;5:e10999 PMCID:PMC2882323

[21]

Pantel K.Tumour microenvironment: informing on minimal residual disease in solid tumours.Nat Rev Clin Oncol2017;14:325-6

[22]

Ferrari S,Picci P.Long-term follow-up and post-relapse survival in patients with non-metastatic osteosarcoma of the extremity treated with neoadjuvant chemotherapy.Ann Oncol1997;8:765-71

[23]

Bielack SS,Delling G.Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols.J Clin Oncol2002;20:776-90

[24]

Smeland S,Whelan J.Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort.Eur J Cancer2019;109:36-50 PMCID:PMC6506906

[25]

Pennati A,Marano G.Autologous fat grafting after sarcoma surgery: evaluation of oncological safety.J Plast Reconstr Aesthet Surg2018;71:1723-9

[26]

Le Nail LR,Rosset P.Comparison of tumor- and bone marrow-derived mesenchymal stromal/stem cells from patients with high-grade osteosarcoma.Int J Mol Sci2018;19:707 PMCID:PMC5877568

[27]

Zhou Z,Kuang M.The CD24+ cell subset promotes invasion and metastasis in human osteosarcoma.EBioMedicine2020;51:102598 PMCID:PMC6948162

[28]

Shao XJ,Chen YQ.Inhibition of M2-like macrophages by all-trans retinoic acid prevents cancer initiation and stemness in osteosarcoma cells.Acta Pharmacol Sin2019;40:1343-50 PMCID:PMC6786412

[29]

Adhikari AS,Wood BM.CD117 and Stro-1 identify osteosarcoma tumor-initiating cells associated with metastasis and drug resistance.Cancer Res2010;70:4602-12 PMCID:PMC3139225

[30]

Tang QL,Xie XB.Enrichment of osteosarcoma stem cells by chemotherapy.Chin J Cancer2011;30:426-32 PMCID:PMC4013417

[31]

Yu L,Zhang C.Enrichment of human osteosarcoma stem cells based on hTERT transcriptional activity.Oncotarget2013;4:2326-38 PMCID:PMC3926830

[32]

Tirino V,d’Aquino R.Detection and characterization of CD133+ cancer stem cells in human solid tumours.PLoS One2008;3:e3469 PMCID:PMC2565108

[33]

Tirino V,Paino F.Human primary bone sarcomas contain CD133+ cancer stem cells displaying high tumorigenicity in vivo.FASEB J2011;25:2022-30

[34]

He A,Huang Y.CD133 expression predicts lung metastasis and poor prognosis in osteosarcoma patients: a clinical and experimental study.Exp Ther Med2012;4:435-41 PMCID:PMC3503795

[35]

Li J,Li ZY.CD133 expression in osteosarcoma and derivation of CD133+ cells.Mol Med Rep2013;7:577-84

[36]

Ozturk S,Gokalp S,Sendemir A.Development and characterization of cancer stem cell-based tumoroids as an osteosarcoma model.Biotechnol Bioeng2020;117:2527-39

[37]

Fujiwara T,Hagiwara K.Clinical relevance and therapeutic significance of microRNA-133a expression profiles and functions in malignant osteosarcoma-initiating cells.Stem Cells2014;32:959-73

[38]

Mardani A,Mousavie SH,Shooshtarizadeh T.Clinical significance of cancer stem cell markers CD133 and CXCR4 in osteosarcomas.Asian Pac J Cancer Prev2020;21:67-73 PMCID:PMC7294029

[39]

Bao Z,Chai D.The expressions of CD133, ALDH1, and vasculogenic mimicry in osteosarcoma and their clinical significance.Int J Clin Exp Pathol2018;11:3656-63 PMCID:PMC6962889

[40]

Tian J,Si M,Li J.CD271+ osteosarcoma cells display stem-like properties.PLoS One2014;9:e98549 PMCID:PMC4043643

[41]

Honoki K,Kubo A.Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance.Oncol Rep2010;24:501-5

[42]

Wang L,Zhang H,Lin CY.Prospective identification of tumorigenic osteosarcoma cancer stem cells in OS99-1 cells based on high aldehyde dehydrogenase activity.Int J Cancer2011;128:294-303

[43]

Martins-Neves SR,Wijers-Koster PM.Chemotherapy induces stemness in osteosarcoma cells through activation of Wnt/β-catenin signaling.Cancer Lett2016;370:286-95

[44]

Wang F,Li Q,Ma C.Untargeted LC-MS/MS analysis reveals metabolomics feature of osteosarcoma stem cell response to methotrexate.Cancer Cell Int2020;20:269 PMCID:PMC7313215

[45]

Mizushima E,Emori M.Osteosarcoma-initiating cells show high aerobic glycolysis and attenuation of oxidative phosphorylation mediated by LIN28B.Cancer Sci2020;111:36-46 PMCID:PMC6942429

[46]

Zhong Z,Lin H,Lin J.Alteration of intracellular metabolome in osteosarcoma stem cells revealed by liquid chromatography-tandem mass spectrometry.Talanta2019;204:6-12

[47]

Koka P,Rangarajan R,Subramanian RK.Uncoupling Warburg effect and stemness in CD133+ve cancer stem cells from Saos-2 (osteosarcoma) cell line under hypoxia.Mol Biol Rep2018;45:1653-62

[48]

Pozzi V,Lucarini G.Cancer stem cell enrichment is associated with enhancement of nicotinamide N-methyltransferase expression.IUBMB Life2020;72:1415-25

[49]

Wang Y,Liang C.Integrated analysis of transcriptome-wide m6A methylome of osteosarcoma stem cells enriched by chemotherapy.Epigenomics2019;11:1693-715

[50]

Menéndez ST,Murillo D,Rodríguez R.Cancer stem cells as a source of drug resistance in bone sarcomas.J Clin Med2021;10:2621 PMCID:PMC8232081

[51]

Belayneh R.The role of aldh in the metastatic potential of osteosarcoma cells and potential ALDH targets. In: Kleinerman ES, Gorlick R, editors. Current advances in the science of osteosarcoma. Cham: Springer International Publishing; 2020. p. 157-66.

[52]

Tsuchida R,Yeger H.Cisplatin treatment increases survival and expansion of a highly tumorigenic side-population fraction by upregulating VEGF/Flt1 autocrine signaling.Oncogene2008;27:3923-34

[53]

Sun DX,Liu KG.Endosialin-expressing bone sarcoma stem-like cells are highly tumor-initiating and invasive.Mol Med Rep2015;12:5665-70 PMCID:PMC4581793

[54]

Di Fiore R,Ferrante RD.Identification and expansion of human osteosarcoma-cancer-stem cells by long-term 3-aminobenzamide treatment.J Cell Physiol2009;219:301-13

[55]

Roundhill EA,Jeys L.RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma.Cell Oncol (Dordr)2021;44:1065-85 PMCID:PMC8516792

[56]

Alfranca A,Tornin J.Bone microenvironment signals in osteosarcoma development.Cell Mol Life Sci2015;72:3097-113

[57]

Danieau G,Rédini F.New insights about Wnt/beta-catenin signaling pathway in primary bone tumors and their microenvironment: a promising target to develop therapeutic strategies?.Int J Mol Sci2019;20:3751 PMCID:PMC6696068

[58]

Deng Q,Che M.Activation of hedgehog signaling in mesenchymal stem cells induces cartilage and bone tumor formation via Wnt/β-Catenin.Elife2019;8:e50208 PMCID:PMC6764825

[59]

Parsons MJ,Dow LE.WNT as a driver and dependency in cancer.Cancer Discov2021;11:2413-29 PMCID:PMC8487948

[60]

Martins-Neves SR,Paiva-Oliveira DI.Osteosarcoma stem cells have active Wnt/β-catenin and overexpress SOX2 and KLF4.J Cell Physiol2016;231:876-86

[61]

Martins-Neves SR,Gomes CMF.Therapy-induced enrichment of cancer stem-like cells in solid human tumors: where do we stand?.Pharmacol Res2018;137:193-204

[62]

Zhang RM,Yu HM.LncRNA DLX6-AS1/miR-129-5p/DLK1 axis aggravates stemness of osteosarcoma through Wnt signaling.Biochem Biophys Res Commun2018;507:260-6

[63]

Jiang C,Wu Z,Xiao J.Histone methyltransferase SETD2 regulates osteosarcoma cell growth and chemosensitivity by suppressing Wnt/β-catenin signaling.Biochem Biophys Res Commun2018;502:382-8

[64]

Blanchard F,Baud’huin M.The dual role of IL-6-type cytokines on bone remodeling and bone tumors.Cytokine Growth Factor Rev2009;20:19-28

[65]

Cortini M,Avnet S,Baldini N.Tumor-activated mesenchymal stromal cells promote osteosarcoma stemness and migratory potential via IL-6 secretion.PLoS One2016;11:e0166500 PMCID:PMC5112800

[66]

Tu B,Liu S.Mesenchymal stem cells promote osteosarcoma cell survival and drug resistance through activation of STAT3.Oncotarget2016;7:48296-308 PMCID:PMC5217018

[67]

Baglio SR,Pérez-Lanzón M.Blocking tumor-educated MSC paracrine activity halts osteosarcoma progression.Clin Cancer Res2017;23:3721-33

[68]

Zhang C,Li WY.Cinobufagin suppresses the characteristics of osteosarcoma cancer cells by inhibiting the IL-6-OPN-STAT3 Pathway.Drug Des Devel Ther2019;13:4075-90 PMCID:PMC6900468

[69]

Tian ZC,Ge H.Apatinib ameliorates doxorubicin-induced migration and cancer stemness of osteosarcoma cells by inhibiting Sox2 via STAT3 signalling.J Orthop Translat2019;22:132-41 PMCID:PMC7231956

[70]

Zhang H,Zheng J.Transforming growth factor β1 signal is crucial for dedifferentiation of cancer cells to cancer stem cells in osteosarcoma.Stem Cells2013;31:433-46

[71]

Ma K,Li W.Gamabufotalin suppressed osteosarcoma stem cells through the TGF-β/periostin/PI3K/AKT pathway.Chem Biol Interact2020;331:109275

[72]

Wang T,Zhang L.The TGFβ-miR-499a-SHKBP1 pathway induces resistance to EGFR inhibitors in osteosarcoma cancer stem cell-like cells.J Exp Clin Cancer Res2019;38:226 PMCID:PMC6540516

[73]

Maurizi G,Gadi A,Basilico C.Sox2 is required for tumor development and cancer cell proliferation in osteosarcoma.Oncogene2018;37:4626-32 PMCID:PMC6195857

[74]

Chen Y,Huang M.MAFB promotes cancer stemness and tumorigenesis in osteosarcoma through a Sox9-mediated positive feedback loop.Cancer Res2020;80:2472-83

[75]

Subramaniam D,Ponnurangam S.Suppressing STAT5 signaling affects osteosarcoma growth and stemness.Cell Death Dis2020;11:149 PMCID:PMC7039889

[76]

Fan H,Zhao C,Yang X.Transcription factor Oct4 promotes osteosarcoma by regulating lncRNA AK055347.Oncol Lett2017;13:396-402 PMCID:PMC5244871

[77]

Xi X,Bao Y.Overexpression of TBL1XR1 confers tumorigenic capability and promotes recurrence of osteosarcoma.Eur J Pharmacol2019;844:259-67

[78]

Chen X,Dang X.Targeting the CtBP1-FOXM1 transcriptional complex with small molecules to overcome MDR1-mediated chemoresistance in osteosarcoma cancer stem cells.J Cancer2021;12:482-97 PMCID:PMC7739006

[79]

Fan GT,He ZW,Zhou GX.Suppressing CHD1L reduces the proliferation and chemoresistance in osteosarcoma.Biochem Biophys Res Commun2021;554:214-21

[80]

Gan Z,Lin S,Shen Z.Knockdown of ubiquitin-specific peptidase 39 inhibited the growth of osteosarcoma cells and induced apoptosis in vitro.Biol Res2017;50:15 PMCID:PMC5389082

[81]

Xu W,Xu R.Knockdown of HuR represses osteosarcoma cells migration, invasion and stemness through inhibition of YAP activation and increases susceptibility to chemotherapeutic agents.Biomed Pharmacother2018;102:587-93

[82]

Li S,Chen X.Soft substrate promotes osteosarcoma cell self-renewal, differentiation, and drug resistance through miR-29b and its target protein spin 1.ACS Biomater Sci Eng2020;6:5588-98

[83]

Zou Y,Yang J,Luo C.miR-34a is downregulated in human osteosarcoma stem-like cells and promotes invasion, tumorigenic ability and self-renewal capacity.Mol Med Rep2017;15:1631-7 PMCID:PMC5364984

[84]

Liang X,Wang W.The DNMT1/miR-34a axis is involved in the stemness of human osteosarcoma cells and derived stem-like cells.Stem Cells Int2019;2019:7028901 PMCID:PMC6875320

[85]

Liang X,Cao X.Isovitexin suppresses cancer stemness property and induces apoptosis of osteosarcoma cells by disruption of the DNMT1/miR-34a/Bcl-2 axis.Cancer Manag Res2019;11:8923-36 PMCID:PMC6800563

[86]

Yao J,He L,Liu Q.TNF-α/miR-155 axis induces the transformation of osteosarcoma cancer stem cells independent of TP53INP1.Gene2020;726:144224

[87]

Guo X,Zhang Z,Gao T.miR-335 negatively regulates osteosarcoma stem cell-like properties by targeting POU5F1.Cancer Cell Int2017;17:29 PMCID:PMC5316195

[88]

Zhang L,Liu Q.KLF8 promotes cancer stem cell-like phenotypes in osteosarcoma through miR-429-SOX2 signaling.Neoplasma2020;67:519-27

[89]

Lavaud M,Ory B.MircoRNA implication in therapeutic resistance and metastatic dissemination of bone-associated tumors. In: Heymann D, editor. Bone cancer: bone sarcomas and bone metastases - from bench to bedside. Academic Press; 2022. p. 447-56.

[90]

Qu Y,Kang M.Knockdown of long non-coding RNA HOXD-AS1 inhibits the progression of osteosarcoma.Biomed Pharmacother2018;98:899-906

[91]

Lu B,He J.Epigenetic profiling identifies LIF as a super-enhancer-controlled regulator of stem cell-like properties in osteosarcoma.Mol Cancer Res2020;18:57-67

[92]

Yan GN,Zhang XC.TSSC3 represses self-renewal of osteosarcoma stem cells and Nanog expression by inhibiting the Src/Akt pathway.Oncotarget2017;8:85628-41 PMCID:PMC5689636

[93]

He J,Liu Z.Functional interplay between long non-coding RNAs and the Wnt signaling cascade in osteosarcoma.Cancer Cell Int2021;21:313 PMCID:PMC8207720

[94]

Camuzard O,Santucci-Darmanin S.Autophagy in osteosarcoma cancer stem cells is critical process which can be targeted by the antipsychotic drug thioridazine.Cancers (Basel)2020;12:3675 PMCID:PMC7762415

[95]

Zhang D,Sun H.Defective autophagy leads to the suppression of stem-like features of CD271+ osteosarcoma cells.J Biomed Sci2016;23:82 PMCID:PMC5116184

[96]

Wang JH,Guo FJ.Knockdown of STIP1 inhibits the invasion of CD133-positive cancer stem-like cells of the osteosarcoma MG63 cell line via the PI3K/Akt and ERK1/2 pathways.Int J Mol Med2020;46:2251-9

[97]

Shu X,Zhen R.Hsp90 inhibitor 17-AAG inhibits stem cell-like properties and chemoresistance in osteosarcoma cells via the Hedgehog signaling pathway.Oncol Rep2020;44:313-24

[98]

Hua Y,Sun M.Plasma membrane proteomic analysis of human osteosarcoma and osteoblastic cells: revealing NDRG1 as a marker for osteosarcoma.Tumour Biol2011;32:1013-21

[99]

Chano T,Avnet S,Baldini N.Prominent role of RAB39A-RXRB axis in cancer development and stemness.Oncotarget2018;9:9852-66 PMCID:PMC5839406

[100]

Takahashi N,Shimizu T.ROCK inhibition induces terminal adipocyte differentiation and suppresses tumorigenesis in chemoresistant osteosarcoma cells.Cancer Res2019;79:3088-99

[101]

Liu F,Li Y.Overexpression of SENP1 reduces the stemness capacity of osteosarcoma stem cells and increases their sensitivity to HSVtk/GCV.Int J Oncol2018; PMCID:PMC6192779

[102]

Tang ML,Li Y,Yang F.MMP-1 Over-expression promotes malignancy and stem-like properties of human osteosarcoma MG-63 cells in vitro.Curr Med Sci2018;38:809-17

[103]

Zhao T,Wang Y.NDRG1 regulates osteosarcoma cells via mediating the mitochondrial function and CSCs differentiation.J Orthop Surg Res2021;16:364 PMCID:PMC8182938

[104]

Feng J,Cai G.TREX1 suppression imparts cancer-stem-cell-like characteristics to CD133- osteosarcoma cells through the activation of E2F4 signaling.Int J Clin Exp Pathol2019;12:1134-53 PMCID:PMC6947077

[105]

Martins-Neves SR,Fontes-Ribeiro C,Cleton-Jansen AM.IWR-1, a tankyrase inhibitor, attenuates Wnt/β-catenin signaling in cancer stem-like cells and inhibits in vivo the growth of a subcutaneous human osteosarcoma xenograft.Cancer Lett2018;414:1-15

[106]

Nomura M,Lee YC.Tegavivint and the β-catenin/ALDH axis in chemotherapy-resistant and metastatic osteosarcoma.J Natl Cancer Inst2019;111:1216-27 PMCID:PMC6855956

[107]

Liu W,Wang Y.Dioscin inhibits stem-cell-like properties and tumor growth of osteosarcoma through Akt/GSK3/β-catenin signaling pathway.Cell Death Dis2018;9:343 PMCID:PMC5832770

[108]

Wei D,Li S.Tideglusib suppresses stem-cell-like features and progression of osteosarcoma by inhibiting GSK-3β/NOTCH1 signaling.Biochem Biophys Res Commun2021;554:206-13

[109]

Wang H,Xu L.Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1α via the PI3K/AKT/mTOR pathway.Oncotarget2016;7:20193-208 PMCID:PMC4991447

[110]

Xiong Q,Wang L.BMP-2 inhibits lung metastasis of osteosarcoma: an early investigation using an orthotopic model.Onco Targets Ther2018;11:7543-53 PMCID:PMC6214601

[111]

Wang S,Zhong B.Bruceine D inhibits tumor growth and stem cell-like traits of osteosarcoma through inhibition of STAT3 signaling pathway.Cancer Med2019;8:7345-58 PMCID:PMC6885873

[112]

Gonçalves JM,Rivero ERC.Inhibition of cancer stem cells promoted by Pimozide.Clin Exp Pharmacol Physiol2019;46:116-25

[113]

Lillo Osuna MA,El Ayachi I.Activation of estrogen receptor alpha by decitabine inhibits osteosarcoma growth and metastasis.Cancer Res2019;79:1054-68 PMCID:PMC6420872

[114]

Hirozane T,Sugano T.Direct conversion of osteosarcoma to adipocytes by targeting TNIK.JCI Insight2021;6:137245 PMCID:PMC7934882

[115]

Qu H,Lian W.Melatonin inhibits osteosarcoma stem cells by suppressing SOX9-mediated signaling.Life Sci2018;207:253-64

[116]

Li Y,Yang B,He Q.Inhibition of KLF4 by statins reverses Adriamycin-induced metastasis and cancer stemness in osteosarcoma cells.Stem Cell Reports2017;8:1617-29 PMCID:PMC5470096

[117]

Deguchi T,Kim S.Metformin preferentially enhances the radio-sensitivity of cancer stem-like cells with highly mitochondrial respiration ability in HMPOS.Mol Ther Oncolytics2021;22:143-51 PMCID:PMC8413836

[118]

Shang D,Guo L,Liu L.Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2.Int J Oncol2017;50:1848-56

[119]

Zhao B,Wang Y.Metformin suppresses self-renewal ability and tumorigenicity of osteosarcoma stem cells via reactive oxygen species-mediated apoptosis and autophagy.Oxid Med Cell Longev2019;2019:9290728 PMCID:PMC6885828

[120]

Paiva-Oliveira DI,Abrunhosa AJ,Gomes CMF.Therapeutic potential of the metabolic modulator Metformin on osteosarcoma cancer stem-like cells.Cancer Chemother Pharmacol2018;81:49-63

[121]

Koh H,Xing Z.Wogonin influences osteosarcoma stem cell stemness through ROS-dependent signaling.In Vivo2020;34:1077-84 PMCID:PMC7279817

[122]

Ba G,Xu N.Novel agent DMAMCL suppresses osteosarcoma growth and decreases the stemness of osteosarcoma stem cell.Cell Cycle2020;19:1530-44 PMCID:PMC7469659

[123]

Dai G,Guo W.Notch pathway inhibition using DAPT, a γ-secretase inhibitor (GSI), enhances the antitumor effect of cisplatin in resistant osteosarcoma.Mol Carcinog2019;58:3-18

[124]

Oka N,Amano H.Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin.Pharmacol Res Perspect2020;8:e00632 PMCID:PMC7387887

[125]

Guo W,Cheng T,Ruan F.The Na+/K+ ATPase inhibitor ouabain attenuates stemness and chemoresistance of osteosarcoma cells.Med Sci Monit2019;25:9426-34 PMCID:PMC6918806

[126]

Gurunathan S,Kang MH.Tangeretin-assisted platinum nanoparticles enhance the apoptotic properties of doxorubicin: combination therapy for osteosarcoma treatment.Nanomaterials (Basel)2019;9:1089 PMCID:PMC6723885

[127]

Ferreira de Oliveira JMP,Coutinho L.Combination of etoposide and fisetin results in anti-cancer efficiency against osteosarcoma cell models.Arch Toxicol2018;92:1205-14

[128]

Heymann MF,Heymann D.Bone sarcomas in the immunotherapy era.Br J Pharmacol2021;178:1955-72

[129]

Mesiano G,Fiorino E.Cytokine Induced Killer cells are effective against sarcoma cancer stem cells spared by chemotherapy and target therapy.Oncoimmunology2018;7:e1465161 PMCID:PMC6208452

[130]

Wang W,Zhu K.SOX2OT variant 7 contributes to the synergistic interaction between EGCG and Doxorubicin to kill osteosarcoma via autophagy and stemness inhibition.J Exp Clin Cancer Res2018;37:37 PMCID:PMC6389193

[131]

Lu SL,Liu GF.Graphene oxide nanoparticle-loaded ginsenoside Rg3 improves photodynamic therapy in inhibiting malignant progression and stemness of osteosarcoma.Front Mol Biosci2021;8:663089 PMCID:PMC8100436

[132]

Tian J,Li Y.CD271 antibody-functionalized HGNs for targeted photothermal therapy of osteosarcoma stem cells.Nanotechnology2020;31:305707

[133]

Mineo PG,Vento F.Salinomycin-loaded PLA nanoparticles: drug quantification by GPC and wave voltammetry and biological studies on osteosarcoma cancer stem cells.Anal Bioanal Chem2020;412:4681-90

[134]

Gui K,Chen F.Lipid-polymer nanoparticles with CD133 aptamers for targeted delivery of all-trans retinoic acid to osteosarcoma initiating cells.Biomed Pharmacother2019;111:751-64

[135]

Chen F,Qi X.Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells.Nanomedicine2018;14:2115-27

[136]

Gambera S,González-Camacho F.Clonal dynamics in osteosarcoma defined by RGB marking.Nat Commun2018;9:3994 PMCID:PMC6162235

[137]

Tellez-Gabriel M,Cadé M,Heymann MF.Circulating tumor cell-derived pre-clinical models for personalized medicine.Cancers (Basel)2018;11:19 PMCID:PMC6356998

[138]

Zhang W,Lin J.Adaptive fibrogenic reprogramming of osteosarcoma stem cells promotes metastatic growth.Cell Rep2018;24:1266-77.e5

[139]

Heymann MF,Heymann D.The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma.Cell Immunol2019;343:103711

[140]

Avnet S,Cortini M.The release of inflammatory mediators from acid-stimulated mesenchymal stromal cells favours tumour invasiveness and metastasis in osteosarcoma.Cancers (Basel)2021;13:5855 PMCID:PMC8616358

[141]

Avnet S,Cortini M,Perut F.Pre-clinical models for studying the interaction between mesenchymal stromal cells and cancer cells and the induction of stemness.Front Oncol2019;9:305 PMCID:PMC6502984

[142]

Bonuccelli G,Grisendi G.Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells.Oncotarget2014;5:7575-88 PMCID:PMC4202145

[143]

Baglio SR,Pérez-Lanzón M.Blocking tumour-educated MSC paracrine activity halts osteosarcoma progression.Clin Cancer Res2017;23:3721-33

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