The role of PTX3 in anti-cancer drug-induced head and neck squamous cell carcinomas dormancy and metastasis

Abstract

Head and neck squamous cell carcinoma (HNSCC) is sixth common cancer in the world Cisplatin has been used for treatment of many human cancers including head and neck ovarian and lung cancers However the anti-cancer drug resistance and metastasis are needed to be solved to improve the overall survival in patients Long pentraxin PTX3 is the regulator of innate immune system that is also associated with tumor metastasis Our previous studies found that the expression level of PTX3 was upregulated in anoikis resistant head and neck squamous carcinoma (HNSCC) cells In this study we want to clarify whether PTX3 plays a role in the regulation of drug resistance and metastasis in post-cisplatin surviving HNSCC cells (CDDP-S cells) We found that the expression of PTX3 was increased in cisplatin-treated tumor cells however the expression of PTX3 was not correlated with the drug resistance in HNSCC The survival cancer cells after cisplatin treatment were more sensitive to epidermal growth factor (EGF) stimulation resulting in enhancement of PTX3 and MMPs expression In addition PTX3 knockdown inhibited EMT markers in EGF-treated cells Trans-well migration and invasion assays further indicated that post-cisplatin surviving cells acquired stronger metastatic ability in EGF-treated cells It is worthy to note that CDDP-S cells not only reduced proliferation ability but also showed the increase of dormancy expressing molecule such as DEC2 BMP4 and NR2F1 indicating the formation of tumor dormancy These results suggest that the increase of PTX3 may confer the sensitivity to EGF-induced metastasis in dormancy CDDP-S cells

Date of Award	2019
Original language	English
Supervisor	Ben-Kuen Chen (Supervisor)