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TP3, an antimicrobial peptide, inhibits infiltration and motility of glioblastoma cells via modulating the tumor microenvironment
- Source :
- Cancer Medicine, Vol 9, Iss 11, Pp 3918-3931 (2020), Cancer Medicine
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Glioblastoma multiforme (GBM) is a cancer of the central nervous system with limited therapeutic outcomes. Infiltrating cancer cells are the contributing factor to high GBM malignancy. The intracranial brain cancer cell infiltration is a complex cascade involving adhesion, migration, and invasion. An arsenal of natural products has been under exploration to overcome GBM malignancy. This study applied the antimicrobial peptide tilapia piscidin 3 (TP3) to GBM8401, U87MG, and T98G cells. The cellular assays and microscopic observations showed that TP3 significantly attenuated cell adhesion, migration, and invasion. A live‐cell video clip showed the inhibition of filopodia protrusions and cell attachment. Probing at the molecular levels showed that the proteolytic activities (from secretion), the mRNA and protein expression levels of matrix metalloproteinases‐2 and ‐9 were attenuated. This result strongly evidenced that both invasion and metastasis were inhibited, although metastatic GBM is rare. Furthermore, the protein expression levels of cell‐mobilization regulators focal adhesion kinase and paxillin were decreased. Similar effects were observed in small GTPase (RAS), phosphorylated protein kinase B (AKT) and MAP kinases such as extracellular signal‐regulated kinases (ERK), JNK, and p38. Overall, TP3 showed promising activities to prevent cell infiltration and metastasis through modulating the tumor microenvironment balance, suggesting that TP3 merits further development for use in GBM treatments.<br />We first describe the anti‐cancer activities of the antimicrobial peptide tilapia piscidin 3 which inhibits infiltration and motility of glioblastoma multiforme cells.
- Subjects :
- Pore Forming Cytotoxic Proteins
0301 basic medicine
MAPK/ERK pathway
Cancer Research
p38 mitogen-activated protein kinases
Apoptosis
infiltration
lcsh:RC254-282
Focal adhesion
glioblastoma multiforme
03 medical and health sciences
0302 clinical medicine
Cell Movement
Biomarkers, Tumor
Tumor Cells, Cultured
Humans
tumor microenvironment
Neoplasm Invasiveness
Radiology, Nuclear Medicine and imaging
Cell adhesion
Protein kinase B
Paxillin
Cell Proliferation
Original Research
Cancer Biology
Tumor microenvironment
biology
Kinase
Chemistry
TP3
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
cell mobility
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
biology.protein
Cancer research
Glioblastoma
Subjects
Details
- ISSN :
- 20457634
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Cancer Medicine
- Accession number :
- edsair.doi.dedup.....199f94ae46fc69fda7dc2c3a5ba24ed0