S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma

Chow, Kin Hoe; Park, Hee Jung; George, Joshy; Yamamoto, Keiko; Gallup, Andrew D.; Graber, Joel H.; Chen, Yuanxin; Jiang, Wen; Steindler, Dennis A.; Neilson, Eric G.; Kim, Betty Y.S.; Yun, Kyuson

doi:10.1158/0008-5472.can-17-1294

Cited by 94 publications

(88 citation statements)

References 45 publications

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“…While knock-down of S100a4 expression and inhibition of S100a4 signaling improves tendon healing, S100a4 can also function in a cell-autonomous manner (31). To determine the effects of S100a4 + cell ablation on tendon healing, we depleted proliferating S100a4 + cells from D5-10 post-surgery (immediately preceding peak S100a4 expression) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cell non-autonomous functions of S100a4 drive fibrotic tendon healing

Ackerman

Studentsova

Best

et al. 2019

Preprint

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29Identification of pro-regenerative approaches to improve tendon healing is of critical importance given 30 the diminished quality of life and physical function that accompanies the typical fibrotic response to 31 tendon injury. S100a4 modulates fibrosis through tissue-type dependent mechanisms, and the role of 32 S100a4 in fibrotic, scar-mediated tendon healing has not been established. In the present study we 33 tested the hypothesis that inhibition of S100a4 improves tendon function following acute injury and 34 surgical repair. We demonstrate cell non-autonomous functions of S100a4 as S100a4 35 haploinsufficiency promotes regenerative tendon healing, including decreased scar formation and 36 improved mechanical properties. Moreover, inhibition of S100a4 via antagonism of its putative 37 receptor, the Receptor for Advanced Glycation Endproducts (RAGE), also decreases scar formation. 38Mechanistically, knock-down of S100a4 decreases myofibroblast and macrophage content at the site of 39 injury, with both cell populations being key drivers of fibrotic progression. In contrast, S100a4 + cell 40 depletion displays time-dependent effects on scar formation, and consistent impairments in restoration 41 of mechanical properties, indicating a critical role for these cells in re-establishing tendon strength after 42 injury. Finally, we demonstrate, that S100a4-lineage cells become α-SMA + myofibroblasts, via loss of 43

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Section: Resultsmentioning

confidence: 99%

Cell non-autonomous functions of S100a4 drive fibrotic tendon healing

Ackerman

Studentsova

Best

et al. 2019

Preprint

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“…GBM is characterized by complex tissue heterogeneity, in which there is a class of stem cell-like tumor-initiating cells, called GSCs, which have the ability to self-renew, grow continuously and differentiate into multiple neural cell types [34][35][36]. Further studies found that GSCs are key factors leading to the occurrence, recurrence, treatment tolerance and poor prognosis of glioma [35,[37][38][39][40]. We successfully propagated eight human GSC lines with four different molecular subtypes and found the highest PSAP expression and secretion in mesenchymal GSCs, as determined by western blotting and ELISA.…”

Section: Discussionmentioning

confidence: 99%

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

Jiang

Zhou

Hou

et al. 2019

The Journal of Pathology

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Mesenchymal glioblastoma (GBM) is the most aggressive subtype of GBM. Our previous study found that neurotrophic factor prosaposin (PSAP) is highly expressed and secreted in glioma and can promote the growth of glioma. The role of PSAP in mesenchymal GBM is still unclear. In this study, bioinformatic analysis, western blotting and RT‐qPCR were used to detect the expression of PSAP in different GBM subtypes. Human glioma cell lines and patient‐derived glioma stem cells were studied in vitro and in vivo, revealing that mesenchymal GBM expressed and secreted the highest level of PSAP among four subtypes of GBM, and PSAP could promote GBM invasion and epithelial–mesenchymal transition (EMT)‐like processes in vivo and in vitro. Bioinformatic analysis and western blotting showed that PSAP mainly played a regulatory role in GBM invasion and EMT‐like processes via the TGF‐β1/Smad signaling pathway. In conclusion, the overexpression and secretion of PSAP may be an important factor causing the high invasiveness of mesenchymal GBM. PSAP is therefore a potential target for the treatment of mesenchymal GBM. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd

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“…The combined gain of S100A4 and loss of membrane E-cadherin in cervical cancer tends to confirm its link with an unfavorable prognosis [8]. Moreover, the role of this biomarker as a central node in a molecular network controlling stemness and EMT has been reported in one of the most aggressive tumors, glioblastoma [9], providing the initial parts of an answer to the question of the relationship between these two processes [10].…”

Section: Introductionmentioning

confidence: 91%

S100A4 Is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma

Nader

Guillon

Petit

et al. 2020

Cancers

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Recent findings suggest that S100A4, a protein involved in communication between stromal cells and cancer cells, could be more involved than previously expected in cancer invasiveness. To investigate its cumulative value in the multistep process of the pathogenesis of malignant mesothelioma (MM), SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra), an advanced and robust technique of quantitative proteomics, was used to analyze a collection of 26 preneoplastic and neoplastic rat mesothelial cell lines and models of MM with increasing invasiveness. Secondly, proteomic and histological analyses were conducted on formalin-fixed paraffin-embedded sections of liver metastases vs. primary tumor, and spleen from tumor-bearing rats vs. controls in the most invasive MM model. We found that S100A4, along with 12 other biomarkers, differentiated neoplastic from preneoplastic mesothelial cell lines, and invasive vs. non-invasive tumor cells in vitro, and MM tumors in vivo. Additionally, S100A4 was the only protein differentiating preneoplastic mesothelial cell lines with sarcomatoid vs. epithelioid morphology in relation to EMT (epithelial-to-mesenchymal transition). Finally, S100A4 was the most significantly increased biomarker in liver metastases vs. primary tumor, and in the spleen colonized by MM cells. Overall, we showed that S100A4 was the only protein that showed increased abundance in all situations, highlighting its crucial role in all stages of MM pathogenesis.

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S100A4 Is a Biomarker and Regulator of Glioma Stem Cells That Is Critical for Mesenchymal Transition in Glioblastoma

Cited by 94 publications

References 45 publications

Cell non-autonomous functions of S100a4 drive fibrotic tendon healing

Cell non-autonomous functions of S100a4 drive fibrotic tendon healing

Prosaposin is a biomarker of mesenchymal glioblastoma and regulates mesenchymal transition through the TGF‐β1/Smad signaling pathway

S100A4 Is a Biomarker of Tumorigenesis, EMT, Invasion, and Colonization of Host Organs in Experimental Malignant Mesothelioma

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