Biochemical and Biophysical Research Communications
Glioma-derived endothelial cells promote glioma cells migration via extracellular vesicles-mediated transfer of MYO1C
Introduction
GBM is a highly vascularized tumor in which the tumor vascular system is abnormal in almost every aspect of its structure and function [1]. Affected by tumor microenvironment, tumor blood vessels and their endothelial cells are significantly different from normal blood vessels and normal endothelial cells in morphology, function, protein expression, and gene level [[2], [3], [4]]. The interaction between tumor cells and stromal cells (such as vascular endothelial cells) plays a vital role in the growth, migration, and metastasis of cancer [[5], [6], [7]]. Previous studies indicated that endothelial cells, peripheral cells and astrocytes could form neurovascular units to support the progression of gliomas [8].
Extracellular vesicles (EV), which diameter is between 50 nm and 1000 nm [9]. It is widely distributed in body fluids and mediates many biological and cellular functions, such as cell-to-cell communication. It can carry and transmit important signal molecules to neighboring cells, such as RNA, proteins, nucleic acids, etc [9]. EV is related to the occurrence and progress of various diseases [10]. It has also been reported that EV is involved in the transmission of information between cells [11], and possess diagnosis and therapeutic potential [12]. There are many articles on RNA components of EV [13], few studies pay attention on proteomics of EV. And the mechanism of EV is very complicated.
Our laboratory previously illustrated that both NhEC-EV and GhEC-EV could promote GSC self-renewal, proliferation and tumor globule formation in vitro, and promote tumor growth in vivo by passing CD9. Nevertheless, NhEC-EV or GhEC-EV could suppress glioma cells (GC) proliferation in vitro [14]. It demonstrates the undifferentiated impact of EV. The purpose of this article is to compare the functionally different effects of GC treated with NhEC-EV and GhEC-EV in order to find a new method to target the elimination of tumor vascular endothelium. We found that MYO1C was specifically expressed in GhEC-EV and promoted GC migration.
Section snippets
Human samples and cell culture
Cerebrospinal fluid (CSF) samples (Glioma, n = 8; Meningioma, n = 1; Schwannoma, n = 1) were provided by Yanwei Liu from Beijing Tiantan Hospital. Primary Human Brain Microvascular Endothelial Cells (ACBRI 376; NhEC) were purchased from Cell systems. Glioma vascular endothelial cells (GhEC) were separated by our lab [14]. EC were maintained in EBM-2 medium containing 2% fetal bovine serum (FBS)-EV-free, 0.1% hydrocortisone, 0.1% R3-IGF, 0.4% hFGF-b, 0.1% VEGF, 0.1% ascorbic acid, 0.1% GA-1000,
Proteomic analysis of GhEC-EV and NhEC-EV
Our lab isolated endothelial cells from glioma tissue previously [14]. Here we named them as glioma human endothelial cells (GhEC). To find differences between GhEC-EV and NhEC-EV. We compared both their appearance and size. Firstly, we detected ALIX, TSG101, CD9, CD63 and Flotillin-1 for EV typical markers, Calnexin for endoplasmic reticulum marker in EC and EC-derived EV (Fig. S1A). Furthermore, EV was identified by Transmission Electron Microscope (TEM) and Nanoparticle-tracking analysis
Discussion
There are significant differences between tumor vascular endothelial cells and normal vascular endothelial cells. Previous studies indicated that brain tumor vascular endothelial cells showed a decrease in tight junction proteins expression (such as claudin-1 and occludin), and an increase in pinocytosis and permeability [18]. Tumor endothelial cells preferred to promote proliferation and motility than normal endothelial cells [19]. These studies suggest that the emergence of vascular
Declaration of competing interest
The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This research was supported by the National Key Research and Development Program of China (2016YFC0902502), the National Sciences Foundation of China (31671316, 21874156), Beijing Nova Program of Science and Technology (Z191100001119137), the CAMS Innovation Fund for Medical Sciences (CIFMS;2016-I2M-1-001, 2017-I2M-2-004, 2017-I2M-3-010). We also thankful to Yanwei Liu from Beijing Tiantan hospital for providing CSF samples.
References (30)
- et al.
Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors
Am. J. Pathol.
(2009) - et al.
Secreted microRNAs: a new form of intercellular communication
Trends Cell Biol.
(2012) - et al.
Isolated tumor endothelial cells maintain specific character during long-term culture
Biochem. Biophys. Res. Commun.
(2010) - et al.
The SHIP2 interactor Myo1c is required for cell migration in 1321 N1 glioblastoma cells
Biochem. Biophys. Res. Commun.
(2016) - et al.
CaMKII-mediated phosphorylation of the myosin motor Myo1c is required for insulin-stimulated GLUT4 translocation in adipocytes
Cell Metabol.
(2008) - et al.
Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases
Nat. Rev. Drug Discov.
(2011) Genes expressed in human tumor endothelium
Science
(2000)- et al.
Altered angiogenesis and survival in human tumor-derived endothelial cells
Faseb. J.
(2003) - et al.
Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis
Nature
(2016) - et al.
Endothelial-cell FAK targeting sensitizes tumours to DNA-damaging therapy
Nature
(2014)
Ets-1 drives breast cancer cell angiogenic potential and interactions between breast cancer and endothelial cells
Int. J. Oncol.
The brain tumor microenvironment
Glia
Shedding light on the cell biology of extracellular vesicles
Nat. Rev. Mol. Cell Biol.
Microvesicles releasing by oral cancer cells enhance endothelial cell angiogenesis via Shh/RhoA signaling pathway
Canc. Biol. Ther.
Extracellular vesicles in diagnosis and therapy of kidney diseases
Am. J. Physiol. Ren. Physiol.
Cited by (6)
Immunomodulatory effects of extracellular vesicles in glioblastoma
2022, Frontiers in Cell and Developmental BiologySignificance of a Tumor Mutation Burden Gene Signature with Prognosis and Immune Feature of Gastric Cancer Patients
2022, International Journal of Genomics