B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role
Abstract
:1. Introduction
2. Results
2.1. Analysis of B7-H3 in MB Exosomes
2.2. B7-H3 Overexpressing Exosomes Contain Novel Pro-Tumorigenic Molecules
2.3. B7-H3 Overexpressing Exosomes Translocate into Stromal and Cancer Cells
3. Discussion
4. Methods
4.1. Antibodies and Reagents
4.2. Cell Lines and Transfections
4.3. Exosome Isolation and Fluorescent Nanoparticle Tracking (NTA)
4.4. Mass Spectrometry and Immunoblotting
4.5. F-Actin Staining
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
EV | Extracellular vesicle |
MB | Medulloblastoma |
B7-H3 | Cluster of Differentiation 276 |
MYC | V-myc avian myelocytomatosis viral oncogene homolog |
DMEM | Dulbecco’s Modified Eagle Media |
FBS | Fetal bovine serum |
HMEC | Human microvascular endothelial cell |
OE | Overexpression |
NTA | Nanoparticle Tracking Analysis |
mL | Milliliter |
μL | Microliter |
min | Minutes |
h | Hours |
References
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Control EV | B7-H3 OE EV | ||||
---|---|---|---|---|---|
Gene | Associated Pathway(s) | Matched Peptide Sequence | Gene | Associated Pathway(s) | Matched Peptide Sequence |
STAT1 | JAK/STAT, IFN-γ/IL-12, Chemokine signaling | DPIQMSMIIYSCLKE | STAT3 | JAK/STAT, Chemokine signaling, Stem cell/LIF, IL-6/HIF-1 | NQGVPVLIVANK |
STAT2 | JAK/STAT, Chemokine signaling | LSLDLEPLLKAGLDLGPELE | c-MYC | MAPK, PI3K/AKT, WNT, TGF-β | KQIVAGVNYFLDVE |
MYCN | Group 4 MB | DAPPQKKIK | AKT2 | MAPK, HIF-1, PI3K/AKT, Chemokine signaling, VEGF, Ras | VSLAKPKHRVTMNE |
IKKB | NF-κB, MAPK, mTOR, PI3K/AKT | AAMMNLLRNNSCLSKMK | MMP2 | Endothelial migration/angiogenesis, MAPK/ERK, Myc | NVAADIAVQLCE, VWELGGCANKE |
TANK | NF-κB, NOD-like receptor | GPQQPIWKPFPNQDSDSVVLSGTDSE | MMP9 | TNF, IL-17/MAPK, NF- κB, angiogenesis | NKPTRPVIVSPANETME |
TGFB1 | TGF-β | LLAPSDSPEWLSFDVTGVVR, RGDLATIHGMNRPFLLLMATPLER | TIMP2 | MMP2/MMP9 | FTTSVVRR |
TGFR1 | TGF-β | VLDDSINMK | NFKB2 | NF-κB, MAPK, PI3K/AKT, Ras | LAPASPMASPGGSIDERPLSSSPLVRVK, LLTDVQLMK, VVNKLIQFLISLVQSNR |
CCL2 | JAK/STAT, Src, MAPK, PI3K/AKT, NF-κB | ICADPKQKWVQDSMDHLDK | IL2 | PI3K/AKT, JAK/STAT, MHC/Antigen signaling, ZAP70 | HPRNIQESPF |
H2A1D | Histone 2 complex | VGAGAPVYLAAVLE | CCL5 | JAK/STAT, PI3K/AKT, TNF, TLR4, LPS/ERK | SSTLIGR |
CCR9 | CCL25, PI3K/AKT, JAK/STAT, RhoA/ROCK, MAPK | LEVLQDCTFE | |||
TSG101 | ESCRT complex, vesicle formation | AMLASRSASLLK | |||
H2A1B | Histone 2 complex | VGAGAPVYLAAVLE |
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Purvis, I.J.; Velpula, K.K.; Guda, M.R.; Nguyen, D.; Tsung, A.J.; Asuthkar, S. B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role. Int. J. Mol. Sci. 2020, 21, 7050. https://doi.org/10.3390/ijms21197050
Purvis IJ, Velpula KK, Guda MR, Nguyen D, Tsung AJ, Asuthkar S. B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role. International Journal of Molecular Sciences. 2020; 21(19):7050. https://doi.org/10.3390/ijms21197050
Chicago/Turabian StylePurvis, Ian J., Kiran K. Velpula, Maheedhara R. Guda, Daniel Nguyen, Andrew J. Tsung, and Swapna Asuthkar. 2020. "B7-H3 in Medulloblastoma-Derived Exosomes; A Novel Tumorigenic Role" International Journal of Molecular Sciences 21, no. 19: 7050. https://doi.org/10.3390/ijms21197050