A subpopulation of cancer stem cells identifies radiographic characteristics in glioblastoma

Cancer stem cells (CSCs), defined by CD133 expression, harbor heterogeneous subpopulations of cells, including endothelial progenitor cells (EPCs). This study aimed to investigate whether a subpopulation of CSCs could affect the radiographic characteristics of glioblastoma. Tissue samples from 10 patients newly diagnosed with glioblastoma were selected according to the radiographic characteristics of their tumors. The patients were divided into two groups based on preoperative magnetic resonance imaging demonstrating contrast enhancement, necrosis and infiltrative patterns: the enhancement/necrosis group (E/N, n=5) and the non-enhancement/infiltration group (NE/I, n=5). Flow cytometry was used to assess the CSCs while immunohistochemistry was used to study microvessel density and the proliferation index. The EPC (CD34+/CD133+) fraction in CSCs (CD133+) was larger in the NE/I group. However, there was little difference in the angiogenic activity assessed using microvessel density between the two groups. The proliferation index (assessed using the antibody Ki-67) was higher in the E/N group and was negatively correlated with the EPC fraction. The non-EPC (CD34−/CD133+) fraction is a major factor responsible for radiographic characteristics of contrast enhancement, thus establishing an association between a subpopulation fraction of CSCs and radiographic characteristics in glioblastoma. Therefore, the simple non-invasive assessment of studying contrast enhancement lesions in glioblastomas may be used to estimate CSC subpopulations.

[1]  G. Zadeh,et al.  MRI biomarkers identify the differential response of glioblastoma multiforme to anti-angiogenic therapy. , 2014, Neuro-oncology.

[2]  Z. Jia,et al.  Early Growth Response 3 (Egr3) Is Highly Over-Expressed in Non-Relapsing Prostate Cancer but Not in Relapsing Prostate Cancer , 2013, PloS one.

[3]  J. Y. Lee,et al.  A distinct subpopulation within CD133 positive brain tumor cells shares characteristics with endothelial progenitor cells. , 2012, Cancer letters.

[4]  R. Shao,et al.  Transdifferentiation of Glioblastoma Stem-Like Cells into Mural Cells Drives Vasculogenic Mimicry in Glioblastomas , 2012, The Journal of Neuroscience.

[5]  Mitchel S Berger,et al.  Regional variation in histopathologic features of tumor specimens from treatment-naive glioblastoma correlates with anatomic and physiologic MR Imaging. , 2012, Neuro-oncology.

[6]  Ryan A. Grant,et al.  Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma. , 2012, Neuro-oncology.

[7]  S. Pastorino,et al.  Transdifferentiation of glioblastoma cells into vascular endothelial cells , 2011, Proceedings of the National Academy of Sciences.

[8]  Rong Wang,et al.  Glioblastoma stem-like cells give rise to tumour endothelium , 2010, Nature.

[9]  R. Bjerkvig,et al.  Immunohistochemical Expression of Stem Cell, Endothelial Cell, and Chemosensitivity Markers in Primary Glioma Spheroids Cultured in Serum‐Containing and Serum‐Free Medium , 2010, Neurosurgery.

[10]  A. Karsan,et al.  Involvement of endothelial progenitor cells in tumor vascularization. , 2010, Microvascular research.

[11]  Dong-Sup Lee,et al.  Clinical and biological implications of CD133-positive and CD133-negative cells in glioblastomas , 2008, Laboratory Investigation.

[12]  S. Bidlingmaier,et al.  The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells , 2008, Journal of Molecular Medicine.

[13]  K. Aldape,et al.  Identification of noninvasive imaging surrogates for brain tumor gene-expression modules , 2008, Proceedings of the National Academy of Sciences.

[14]  C. Decaestecker,et al.  Apparent Diffusion Coefficient and Cerebral Blood Volume in Brain Gliomas: Relation to Tumor Cell Density and Tumor Microvessel Density Based on Stereotactic Biopsies , 2008, American Journal of Neuroradiology.

[15]  Jian Wang,et al.  CD133 negative glioma cells form tumors in nude rats and give rise to CD133 positive cells , 2008, International journal of cancer.

[16]  Peter Canoll,et al.  Identification of A2B5+CD133- tumor-initiating cells in adult human gliomas. , 2008, Neurosurgery.

[17]  Alexander Brawanski,et al.  CD133(+) and CD133(-) glioblastoma-derived cancer stem cells show differential growth characteristics and molecular profiles. , 2007, Cancer research.

[18]  Lijun Xue,et al.  Metastasis-Suppressing Potential of Ribonucleotide Reductase Small Subunit p53R2 in Human Cancer Cells , 2006, Clinical Cancer Research.

[19]  R M Weisskoff,et al.  Relative cerebral blood volume maps corrected for contrast agent extravasation significantly correlate with glioma tumor grade, whereas uncorrected maps do not. , 2006, AJNR. American journal of neuroradiology.

[20]  Tracy T Batchelor,et al.  Magnetic Resonance Imaging Characteristics Predict Epidermal Growth Factor Receptor Amplification Status in Glioblastoma , 2005, Clinical Cancer Research.

[21]  R. Henkelman,et al.  Identification of human brain tumour initiating cells , 2004, Nature.

[22]  P. Dirks,et al.  Cancer stem cells in nervous system tumors , 2004, Oncogene.

[23]  D. Ribatti.  The involvement of endothelial progenitor cells in tumor angiogenesis , 2004, Journal of cellular and molecular medicine.

[24]  Glyn Johnson,et al.  Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study. , 2002, Radiology.

[25]  K. Okamoto,et al.  MRI of high-grade astrocytic tumors: early appearance and evolution , 2002, Neuroradiology.

[26]  S. Rafii,et al.  The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1. , 1998, Blood.

[27]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[28]  L. Ricci-Vitiani,et al.  Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells , 2011, Nature.

[29]  Ronald Simon,et al.  Immunohistochemical analysis of tissue microarrays. , 2010, Methods in molecular biology.

[30]  T. Yonezawa,et al.  Early appearance of high grade glioma on magnetic resonance imaging. , 2009, Neurologia medico-chirurgica.

[31]  E. Sternberg,et al.  Flow cytometry as a tool for measurement of steroid hormone receptor protein expression in leukocytes. , 2009, Methods in molecular biology.