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

• Published in: BMC cancer Vol. 21; no. 1; p. 1283
• Main Authors: Pu, Yinfei, Li, Qingxiang, Wang, Yifei, Xu, Le, Qiao, Qiao, Guo, Yuxing, Guo, Chuanbin
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01-12-2021; BioMed Central; BMC
• Subjects: Animal models; Animals; Antibodies; Antineoplastic Agents - therapeutic use; Breast cancer; Cancer cells; Cancer invasiveness; Cancer therapies; Cell Communication; Cell migration; Cell Movement; Cell viability; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin - therapeutic use; Development and progression; Drug resistance; Drug Resistance, Neoplasm; Drug therapy; eIF-2 Kinase - metabolism; Extracellular signal-regulated kinases; Female; Gene Expression; Health aspects; Heterografts; Humans; IL8, CD10, p-ERK; Immunohistochemistry; Interleukin 8; Interleukin-8 - antagonists & inhibitors; Interleukin-8 - metabolism; Laboratory animals; Magnetic fields; Mesenchyme; Metabolic pathways; Metastasis; Mice; Mice, Inbred BALB C; Mice, Nude; Microspheres; Mouth cancer; Mouth Neoplasms - drug therapy; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; mRNA; Neoplasm Invasiveness; Neoplasm Transplantation; Neoplastic Stem Cells; Neprilysin - metabolism; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Physiological aspects; Proteins; Radiation therapy; Reagents; Signal Transduction; Spheroids, Cellular - pathology; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - pathology; Stem cell transplantation; Stem cells; Tumor cell lines; Xenografts; China; United States > US; IL8, CD10, p-ERK; Oral squamous cell carcinoma; Drug resistance; Cisplatin
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-09025-7

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.
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.
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.
IL8 secretion by CD10 positive cells promotes migration, invasion, and cisplatin resistance of OSCC via the p-ERK signaling pathway.