Tal Shahar1,2, Uri Rozovski3, Kenneth R Hess4, Anwar Hossain1,2, Joy Gumin1,2, Feng Gao1,2, Gregory N Fuller5, Lindsey Goodman6, Erik P Sulman6, Frederick F Lang1,2. 1. Department of Neurosurgery, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 2. Brain Tumor Center, Unit 442, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 3. Department of Leukemia, Unit 428, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 4. Department of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 5. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA. 6. Department of Radiation Oncology, Unit 97, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Abstract
Background: Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in human gliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method: We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database. Results: In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P = .04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P = .04), respectively. Conclusions: The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas.
Background: Human mesenchymal stem cells (hMSCs) have been shown to reside as stromal cells in humangliomas as glioma-associated hMSCs (GA-hMSCs), but their biological role remains unclear. Because recent evidence indicates that GA-hMSCs drive tumor cell proliferation and stemness, we hypothesized that a higher percentage of GA-hMSCs in tumors predicts poor patient prognosis. Method: We determined the percentage of cells coexpressing GA-hMSC markers CD105+/CD73+/CD90+ from patients with newly diagnosed high-grade glioma and analyzed the association between this percentage and overall survival (OS) in 3 independent cohorts: fresh surgical glioblastoma specimens (cohort 1, N = 9), cultured tumor specimens at passage 3 (cohort 2, N = 28), and The Cancer Genome Atlas (TCGA) database. Results: In all cohorts, patient OS correlated with the percentages of GA-hMSCs in tumors. For cohort 1, the median OS of patients with tumors with a low percentage of triple-positive cells was 46 months, and for tumors with a high percentage of triple-positive cells, it was 12 months (hazard ratio [HR] = 0.24; 95% CI: 0.02-0.5, P = .02). For cohort 2, the median OS of patients with tumors with a low percentage of GA-hMSCs was 66 months, and for tumors with a high percentage, it was 11 months (HR = 0.38; 95% CI: 0.13-0.9, P = .04). In the database of TCGA, the median OS times in patients with high and low coexpression levels of CD105/CD73/CD90 were 8.4 months and 13.1 months (HR = 0.4; 95% CI: 0.1-0.88; P = .04), respectively. Conclusions: The percentage of GA-MSCs inversely correlates with OS, suggesting a role for GA-MSCs in promoting aggressive behavior of gliomas.
Authors: Seth B Coffelt; Frank C Marini; Keri Watson; Kevin J Zwezdaryk; Jennifer L Dembinski; Heather L LaMarca; Suzanne L Tomchuck; Kerstin Honer zu Bentrup; Elizabeth S Danka; Sarah L Henkle; Aline B Scandurro Journal: Proc Natl Acad Sci U S A Date: 2009-02-20 Impact factor: 11.205
Authors: W J Curran; C B Scott; J Horton; J S Nelson; A S Weinstein; A J Fischbach; C H Chang; M Rotman; S O Asbell; R E Krisch Journal: J Natl Cancer Inst Date: 1993-05-05 Impact factor: 13.506
Authors: Aarif Y Khakoo; Shibani Pati; Stasia A Anderson; William Reid; Mohamed F Elshal; Ilsa I Rovira; Ahn T Nguyen; Daniela Malide; Christian A Combs; Gentzon Hall; Jianhu Zhang; Mark Raffeld; Terry B Rogers; William Stetler-Stevenson; Joseph A Frank; Marvin Reitz; Toren Finkel Journal: J Exp Med Date: 2006-04-24 Impact factor: 14.307
Authors: Anne Clavreul; Milad Pourbaghi-Masouleh; Emilie Roger; Nolwenn Lautram; Claudia N Montero-Menei; Philippe Menei Journal: J Exp Clin Cancer Res Date: 2017-09-29