Mesenchymal Stem-Like Cells Derived from the Ventricle More Effectively Enhance Invasiveness of Glioblastoma Than Those Derived from the Tumor
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM pa tient-derived cells. Materials and Methods: The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo ex periments. Results: After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investi gated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accel erated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLC induced increases in the invasiveness of GBM TSs. Conclusion: Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates.
Abstract
Purpose: Glioblastoma (GBM) is one of the most lethal human tumors with a highly infiltrative phenotype. Our previous studies showed that GBM originates in the subventricular zone, and that tumor-derived mesenchymal stem-like cells (tMSLCs) promote the invasiveness of GBM tumorspheres (TSs). Here, we extend these studies in terms of ventricles using several types of GBM pa tient-derived cells. Materials and Methods: The invasiveness of GBM TSs and ventricle spheres (VSs) were quantified via collagen-based 3D invasion assays. Gene expression profiles were obtained from microarray data. A mouse orthotopic xenograft model was used for in vivo ex periments. Results: After molecular and functional characterization of ventricle-derived mesenchymal stem-like cells (vMSLCs), we investi gated the effects of these cells on the invasiveness of GBM TSs. We found that vMSLC-conditioned media (CM) significantly accel erated the invasiveness of GBM TSs and VSs, compared to the control and even tMSLC-CM. Transcriptome analyses revealed that vMSLC secreted significantly higher levels of several invasiveness-associated cytokines. Moreover, differentially expressed genes between vMSLCs and tMSLCs were enriched for migration, adhesion, and chemotaxis-related gene sets, providing a mechanistic basis for vMSLC-induced invasion of GBM TSs. In vivo experiments using a mouse orthotopic xenograft model confirmed vMSLC induced increases in the invasiveness of GBM TSs. Conclusion: Although vMSLCs are non-tumorigenic, this study adds to our understanding of how GBM cells acquire infiltrative features by vMSLCs, which are present in the region where GBM genesis originates.
참고문헌 (37)
- Hoshide R, "2016 World Health Organization classification of central nervous system tumors : an era of molecular biology", World Neurosurg, 94, pp.561~562 (2016)
- Stupp R, "Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study : 5-year analysis of the EORTCNCIC trial", Lancet Oncol, 10, pp.459~466 (2009)
- Roh TH, "Long-term outcomes of concomitant chemoradiotherapy with temozolomide for newly diagnosed glioblastoma patients : a singlecenter analysis", Medicine(Baltimore), 96, pp.e7422~ (2017)
- Roh TH, "Survival benefit of lobectomy over gross-total resection without lobectomy in cases of glioblastoma in the noneloquent area : a retrospective study", J Neurosurg, 132, pp.895~901 (2020)
- Auffinger B, "The role of glioma stem cells in chemotherapy resistance and glioblastoma multiforme recurrence", Expert Rev Neurother, 15, pp.741~752 (2015)
- Jeong H, "Combined treatment with 2'-hydroxycinnamaldehyde and temozolomide suppresses glioblastoma tumorspheres by decreasing stemness and invasiveness", J Neurooncol, 143, pp.69~77 (2019)
- Jackson M, "Glioblastoma stem-like cells : at the root of tumor recurrence and a therapeutic target", Carcinogenesis, 36, pp.177~185 (2015)
- 강석구, "Potential use of glioblastoma tumorsphere: clinical credentialing", Archives of Pharmacal Research, 38(3), pp.402~407 (2015), 대한약학회
- Patrizii M, "Utility of glioblastoma patient-derived orthotopic xenografts in drug discovery and personalized therapy", Front Oncol, 8, pp.23~ (2018)
- Kong BH, "Isolation of glioma cancer stem cells in relation to histological grades in glioma specimens", Childs Nerv Syst, 29, pp.217~229 (2013)
- Kim KM, "Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments", Cancer Cell Int, 16, pp.43~ (2016)
- Park J, "Regulation of bioenergetics through dual inhibition of aldehyde dehydrogenase and mitochondrial complex I suppresses glioblastoma tumorspheres", Neuro Oncol, 20, pp.954~965 (2018)
- Thomas AA, "Emerging therapies for glioblastoma", JAMA Neurol, 71, pp.1437~1444 (2014)
- Behnan J, "Recruited brain tumor-derived mesenchymal stem cells contribute to brain tumor progression", Stem Cells, 32, pp.1110~1123 (2014)
- Li L, "Cancer stem cell and stromal microenvironment", Ochsner J, 13, pp.109~118 (2013)
- Valkenburg KC, "Targeting the tumour stroma to improve cancer therapy", Nat Rev Clin Oncol, 15, pp.366~381 (2018)
- Kim YG, "Existence of glioma stroma mesenchymal stemlike cells in Korean glioma specimens", Childs Nerv Syst, 29, pp.549~563 (2013)
- Kong BH, "Increased in vivo angiogenic effect of glioma stromal mesenchymal stem-like cells on glioma cancer stem cells from patients with glioblastoma", Int J Oncol, 42, pp.1754~1762 (2013)
- Lim EJ, "Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells", Oncotarget, 8, pp.1438~1448 (2017)
- Lim EJ, "Crosstalk between GBM cells and mesenchymal stemlike cells promotes the invasiveness of GBM through the C5a", p38, Neuro Oncol, pp.2020, 22[DOI]
- Yoon SJ, "Tumor mesenchymal stem-like cell as a prognostic marker in primary glioblastoma", Stem Cells Int, 2016, pp.6756983~ (2016)
- Moon JH, "Histopathological implications of ventricle wall 5-aminolevulinic acid-induced fluorescence in the absence of tumor involvement on magnetic resonance images", Oncol Rep, 36, pp.837~844 (2016)
- Lee JH, "Human glioblastoma arises from subventricular zone cells with low-level driver mutations", Nature, 560, pp.243~247 (2018)
- 윤선진, "Glioblastoma Cellular Origin and the Firework Pattern of Cancer Genesis from the Subventricular Zone", 대한신경외과학회지, 63(1), pp.26~33 (2020), 대한신경외과학회
- Oh HC, "Combined effects of niclosamide and temozolomide against human glioblastoma tumorspheres", J Cancer Res Clin Oncol, 146, pp.2817~2828 (2020)
- Kim EH, "Inhibition of glioblastoma tumorspheres by combined treatment with 2-deoxyglucose and metformin", Neuro Oncol, 19, pp.197~207 (2017)
- Du P, "Lumi : a pipeline for processing Illumina microarray", Bioinformatics, 24, pp.1547~1548 (2008)
- Bindea G, "ClueGO : a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks", Bioinformatics, 25, pp.1091~1093 (2009)
- Dominici M, "Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement", Cytotherapy, 8, pp.315~317 (2006)
- Kang SG, "Isolation and perivascular localization of mesenchymal stem cells from mouse brain", Neurosurgery, 67, pp.711~720 (2010)
- Lee J, "Identification of phenotype deterministic genes using systemic analysis of transcriptional response", Sci Rep, 4, pp.4413~ (2014)
- Karnoub AE, "Mesenchymal stem cells within tumour stroma promote breast cancer metastasis", Nature, 449, pp.557~563 (2007)
- Shinagawa K, "Mesenchymal stem cells enhance growth and metastasis of colon cancer", Int J Cancer, 127, pp.2323~2333 (2010)
- Hanahan D, "Hallmarks of cancer : the next generation", Cell, 144, pp.646~674 (2011)
- Kwiatkowska A, "Signaling determinants of glioma cell invasion", Adv Exp Med Biol, 1202, pp.129~149 (2020)
- Park J, "Transcriptome profiling-based identification of prognostic subtypes and multi-omics signatures of glioblastoma", Sci Rep, 9, pp.10555~ (2019)
- Brandes AA, "MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients", J Clin Oncol, 26, pp.2192~2197 (2008)