DSPP-MMP20 gene silencing downregulates cancer stem cell markers in human oral cancer cells

Autor: Kalu U.E. Ogbureke, Ioannis Gkouveris, Jaya Aseervatham, Nikolaos G. Nikitakis, Kelvin Barahona
Rok vydání: 2018
Předmět:
0301 basic medicine
MMP20
Biochemistry
0302 clinical medicine
ATP Binding Cassette Transporter
Subfamily G
Member 2
RNA
Small Interfering
Mouth neoplasm
Extracellular Matrix Proteins
education.field_of_study
lcsh:Cytology
Cancer stem cells
DSPP
Up-Regulation
Hyaluronan Receptors
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Oral Cancer
Mouth Neoplasms
RNA Interference
OSCC
Cancer stem cell markers
medicine.drug
Sialoglycoproteins
Population
Short Report
Down-Regulation
Antineoplastic Agents
Biology
03 medical and health sciences
stomatognathic system
Downregulation and upregulation
Cancer stem cell
Cell Line
Tumor
Biomarkers
Tumor
medicine
Humans
Gene silencing
lcsh:QH573-671
education
Molecular Biology
Cisplatin
CD44
Cell Biology
Phosphoproteins
stomatognathic diseases
Matrix Metalloproteinase 20
030104 developmental biology
Cancer cell
Cancer research
biology.protein
Zdroj: Cellular & Molecular Biology Letters
Cellular & Molecular Biology Letters, Vol 23, Iss 1, Pp 1-14 (2018)
ISSN: 1689-1392
1425-8153
DOI: 10.1186/s11658-018-0096-y
Popis: Background Recent findings indicate that dentin sialophosphoprotein (DSPP) and matrix metalloproteinase (MMP) 20 interact in oral squamous cell carcinoma (OSCC). The objective of this study was to determine the effects of DSPP/MMP20 gene silencing on oral cancer stem cell (OCSC) markers. Methods The expression of well-established OCSC markers: ABCG2; ALDH1; CD133; CD44; BMI1; LGR4, and Podoplanin in DSPP/MMP20-silenced OSCC cell line, OSC2, and controls were assayed by western blot (WB), and flow cytometry techniques. The sensitivity of OSC2 cells to cisplatin following DSPP/MMP20 silencing was also determined. Results DSPP/MMP20 silencing resulted in downregulation of OCSC markers, more profoundly ABCG2 (84%) and CD44 (81%), following double silencing. Furthermore, while treatment of parent (pre-silenced) OSC2 cells with cisplatin resulted in upregulation of OCSC markers, DSPP/MMP20-silenced OSC2 cells similarly treated resulted in profound downregulation of OCSC markers (72 to 94% at 50 μM of cisplatin), and a marked reduction in the proportion of ABCG2 and ALDH1 positive cells (~ 1%). Conclusions We conclude that the downregulation of OCSC markers may signal a reduction in OCSC population following MMP20/DSPP silencing in OSCC cells, while also increasing their sensitivity to cisplatin. Thus, our findings suggest a potential role for DSPP and MMP20 in sustaining OCSC population in OSCCs, possibly, through mechanism(s) that alter OCSC sensitivity to treatment with chemotherapeutic agents such as cisplatin. Electronic supplementary material The online version of this article (10.1186/s11658-018-0096-y) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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