pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells

Abstract Background Cancer stem cells (CSCs) drive tumor initiation and progression and participate in tumor chemoresistance. We recently discovered that oral squamous cell carcinoma (OSCC) cells that highly express CD10 (CD10H cells) present cancer stem cells (CSC)-associated characteristics, which...

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Autores principales: Yinfei Pu, Qingxiang Li, Yifei Wang, Le Xu, Qiao Qiao, Yuxing Guo, Chuanbin Guo
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Publicado: BMC 2021
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spelling oai:doaj.org-article:72645804ed624fdfadd04be79ad138452021-12-05T12:19:39ZpERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells10.1186/s12885-021-09025-71471-2407https://doaj.org/article/72645804ed624fdfadd04be79ad138452021-12-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-09025-7https://doaj.org/toc/1471-2407Abstract Background Cancer stem cells (CSCs) drive tumor initiation and progression and participate in tumor chemoresistance. We recently discovered that oral squamous cell carcinoma (OSCC) cells that highly express CD10 (CD10H cells) present cancer stem cells (CSC)-associated characteristics, which, in turn, affect the tumor growth, epithelial-mesenchymal transition (EMT), and resistance to cisplatin. In this study, we further investigated this mechanism in vitro and in vivo. We hypothesized that IL8 might regulate migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells through the ERK pathway. Methods CD10 MicroBead Kit was used to select HN6 cells with high and low expression of CD10. The target protein IL8 was screened via protein chip assay. Lentiviral transduction and specific inhibitor were applied to investigate the signaling pathway. Real-time PCR, Western blot, and immunohistochemistry were used to analyze the mRNA and protein expression; transwell assay, spheroid formation assay, and cell viability assay were used to study the cell biological behavior in vitro; xenograft animal model was used to evaluate the tumor formation rate in vivo. Results Overexpression of CD10 promoted CSC-related genes expression and enhanced migration, invasion, spheroid formation, and chemoresistance in HN6 cells. Moreover, the overexpression of IL8 was detected in OSCC tumor tissue and cell lines (HN6 and CAL27) overexpressing CD10. IL8 secreted by CD10H HN6 promoted migration and invasion and restored tumor chemosensitivity via the p-ERK signaling pathway, while the inhibition of IL8 increased the chemosensitivity to cisplatin. Conclusions IL8 secretion by CD10 positive cells promotes migration, invasion, and cisplatin resistance of OSCC via the p-ERK signaling pathway.Yinfei PuQingxiang LiYifei WangLe XuQiao QiaoYuxing GuoChuanbin GuoBMCarticleIL8, CD10, p-ERKOral squamous cell carcinomaDrug resistanceCisplatinNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-10 (2021)
institution DOAJ
collection DOAJ
language EN
topic IL8, CD10, p-ERK
Oral squamous cell carcinoma
Drug resistance
Cisplatin
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle IL8, CD10, p-ERK
Oral squamous cell carcinoma
Drug resistance
Cisplatin
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Yinfei Pu
Qingxiang Li
Yifei Wang
Le Xu
Qiao Qiao
Yuxing Guo
Chuanbin Guo
pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells
description Abstract Background Cancer stem cells (CSCs) drive tumor initiation and progression and participate in tumor chemoresistance. We recently discovered that oral squamous cell carcinoma (OSCC) cells that highly express CD10 (CD10H cells) present cancer stem cells (CSC)-associated characteristics, which, in turn, affect the tumor growth, epithelial-mesenchymal transition (EMT), and resistance to cisplatin. In this study, we further investigated this mechanism in vitro and in vivo. We hypothesized that IL8 might regulate migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells through the ERK pathway. Methods CD10 MicroBead Kit was used to select HN6 cells with high and low expression of CD10. The target protein IL8 was screened via protein chip assay. Lentiviral transduction and specific inhibitor were applied to investigate the signaling pathway. Real-time PCR, Western blot, and immunohistochemistry were used to analyze the mRNA and protein expression; transwell assay, spheroid formation assay, and cell viability assay were used to study the cell biological behavior in vitro; xenograft animal model was used to evaluate the tumor formation rate in vivo. Results Overexpression of CD10 promoted CSC-related genes expression and enhanced migration, invasion, spheroid formation, and chemoresistance in HN6 cells. Moreover, the overexpression of IL8 was detected in OSCC tumor tissue and cell lines (HN6 and CAL27) overexpressing CD10. IL8 secreted by CD10H HN6 promoted migration and invasion and restored tumor chemosensitivity via the p-ERK signaling pathway, while the inhibition of IL8 increased the chemosensitivity to cisplatin. Conclusions IL8 secretion by CD10 positive cells promotes migration, invasion, and cisplatin resistance of OSCC via the p-ERK signaling pathway.
format article
author Yinfei Pu
Qingxiang Li
Yifei Wang
Le Xu
Qiao Qiao
Yuxing Guo
Chuanbin Guo
author_facet Yinfei Pu
Qingxiang Li
Yifei Wang
Le Xu
Qiao Qiao
Yuxing Guo
Chuanbin Guo
author_sort Yinfei Pu
title pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells
title_short pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells
title_full pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells
title_fullStr pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells
title_full_unstemmed pERK-mediated IL8 secretion can enhance the migration, invasion, and cisplatin resistance of CD10-positive oral cancer cells
title_sort perk-mediated il8 secretion can enhance the migration, invasion, and cisplatin resistance of cd10-positive oral cancer cells
publisher BMC
publishDate 2021
url https://doaj.org/article/72645804ed624fdfadd04be79ad13845
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