Existence of glioma stroma mesenchymal stemlike cells in Korean glioma specimens

Kim, Young Goo; Jeon, Soyoun; Sin, Ga Yeong; Shim, Jae Yong; Kim, Bo Kyung; Shin, Hye Jin; Lee, Ji Hyun; Huh, Yong Min; Lee, Su Jae; Kim, Eui Hyun; Park, Eun Kyung; Kim, Se Hoon; Chang, Jong Hee; Kim, Do Kyung; Kim, Sun Ho; Hong, Yong Kil; Kang, Seok‐Gu; Lang, Frederick F.

doi:10.1007/s00381-012-1988-1

Cited by 26 publications

(56 citation statements)

References 53 publications

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“…In line with this trend, tMSLCs are recently defined as stromal cells interacting with GBM cells and their potential role in tumor progression has received intensive attention [11, 12, 23–25]. …”

Section: Discussionmentioning

confidence: 99%

“…tMSLC09-03 (previously referred as KGS-MSC05-04) have been isolated from biopsy of GBM patient [23]. All non-adherent cells were washed away with phosphate-buffered saline (PBS) and only adherent tMSLCs were cultured in MEMα (Mediatech) containing 10% FBS (Lonza), 2 mM L-glutamine (Mediatech), and antibiotic–antimycotic solution (Gibco, Seoul, Korea).…”

Section: Methodsmentioning

confidence: 99%

“…Mice were housed in microisolator cages under sterile conditions and observed for at least 1 week before study initiation to ensure proper health. GBM cells alone or combined with tMSLC0903 (1:1 ratio) were injected at a speed of 0.5 μl/min into the right frontal lobe of mouse skull via a Hamilton syringe (Dongwoo Science Co., Seoul, Korea) using a guide-screw system, as described previously [23, 36, 37]. …”

Section: Methodsmentioning

confidence: 99%

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Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells

et al. 2016

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Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GBM) cells. However, the cellular mechanism underlying HA-rich microenvironment in GBM remains unexplored. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) contribute to abundance of hyaluronic acid (HA) in tumor microenvironment through HA synthase-2 (HAS2) induction, and thereby enhances invasiveness of GBM cells. In an autocrine manner, C5a secreted by tMSLCs activated ERK MAPK for HAS2 induction in tMSLCs. Importantly, HA acted as a signaling ligand of its cognate receptor RHAMM for intracellular signaling activation underlying invasiveness of GBM cells. Taken together, our study suggests that tMSLCs contribute to HA-rich proinvasive ECM microenvironment in GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells

et al. 2016

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“…These latter may arise from normal progenitors, in analogy with what occurs in Platelet‐Derived Growth Factor (PDGF)‐induced gliomas of the adult or neonatal rat, where a small population of neural stem cells are “recruited” into the glioma and are induced to proliferate . Accordingly, Kong's group has isolated from a single glioblastoma patient a stem cell line with some mesenchymal features (GS‐MSLC) that showed the ability to influence a GSC line by increasing, in vitro, its proliferation, and, in vivo, the size of the formed tumors via an incremented angiogenesis . Our article newly shows that normal stem cells with mesenchymal features and a wide differentiation potential can be isolated both from LGG and HGG, support tumor growth releasing exosomes, and can predict patient prognosis.…”

Section: Discussionmentioning

confidence: 99%

Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas

et al. 2014

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Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low-grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state-of-theart markers, hindering the decision-making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high-grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma-associated stem cells (GASC) from LGG (n540) and HGG (n573). GASC showed stem cell features, anchorage-independent growth, and supported the malignant properties of both A172 cells and human glioma-stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n513) and LGG (n512) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG-patients. At the multivariate Cox analysis, the GASCbased score was the only independent predictor of overall survival and malignant progression free-survival. Conclusions: The microenvironment of both LGG and HGG hosts non-tumorigenic multipotent stem cells that can increase in vitro the biological aggressiveness of gliomainitiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patientbased approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma.

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“…However, CD90 expression has also been observed in stromal cells (e.g. mesenchymal stem cells (MSC), cancer-associated fibroblasts (CAF), and endothelium) of various cancers, and plays an important role in disease progression [23-27]. …”

Section: Introductionmentioning

confidence: 99%

Heterogeneity of The CD90+ Population in Different Stages of Hepatocarcinogenesis

Thakolwiboon

Zhu

Liang

et al. 2014

J Proteomics Bioinform

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We have characterized herein the heterogeneity of the CD90+ population at each stage of hepatocarcinogenesis using a computer-assisted immunohistochemical staining evaluation method for quantitative analysis on tissue microarrays. We found that CD90 in Hepatocellular carcinoma (HCC) tissues, which has been shown to be a marker for cancer stem cells, is expressed on tumor cells, in the stroma or on endothelial cells. Sub-classification of the CD90+ population was based on morphology and co-expression with known markers including CD45 and CD31. Multiple linear regression suggested that the percentage of CD90+ cancer cells/hepatocyte (p<0.0001), level of overall CD90 expression (p<0.0014), and level of CD90 expression in tumor islands (p<0.0001) increased significantly in each stage of liver disease progression, while the level of stromal CD90 expression (p=0.1129) did not change significantly. Additionally, only the CD90+ cancer cells were positive for other cancer stem cell (CSC) markers including CD24, CD44 and CD133 whereas the other CD90+ cells were negative for these markers. CD90 expression in cirrhosis was observed in hepatocytes, the portal tract area and fibrous septa while CD90 expression in normal liver was limited only to the portal tract area. This study demonstrates the heterogeneity of the CD90+ population in HCC where a small population of the CD90+ cells that expressed other CSC markers are CSCs and are associated with advanced stages of hepatocarcinogenesis. This heterogeneity should be emphasized in further studies where other methods may not be able to discriminate these distinct types of CD90+ cells.

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Existence of glioma stroma mesenchymal stemlike cells in Korean glioma specimens

Cited by 26 publications

References 53 publications

Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells

Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells

Glioma‐Associated Stem Cells: A Novel Class of Tumor‐Supporting Cells Able to Predict Prognosis of Human Low‐Grade Gliomas

Heterogeneity of The CD90+ Population in Different Stages of Hepatocarcinogenesis

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