Identification of important cancer stem cell CSC markers and dissect their role in invasion and drug resistance of oral squamous cell carcinoma OSCC

Abstract

newline Background: Oral squamous cell carcinoma (OSCC) is one of the most prevalent newlinecancers, with an increasing number of new cases worldwide. Small subsets of self- newlinerenewal cells, referred to as oral cancer stem cells (OCSCs) are difficult to treat. newlineThese cells are accountable for OSCC severity with tumor progression, newlinemigration/invasion, drug resistance, and cause cancer recurrence. Detailed knowledge newlineof these OCSCs is crucial to tackling this neoplasm. Our extensive literature search newlinegave us an idea about the cell-surface glycoprotein (CD44), cytoplasmic aldehyde newlinedehydrogenases (ALDH, particularly ALDH-1A1/-3A1 isotypes) and nuclear newlinetranscription factor Nanog are important, but their regulation is not clearly newlineunderstood. Cisplatin-resistant (CisR) oral tumor recur frequently, CisR-OSCC cells newlineacquire stem-like characteristics and are difficult to treat. This thesis aims to newlinedetermine the role/ regulation of CD44, Nanog, ALDH towards the OSCC severity newlineand determine and stemness. newlineMethods: In the present study, one hundred forty-five fresh human OSCC tissue newlinespecimens, including 18 adjacent normal, 42 noninvasive (N0), 53 invasive tumor newlinesamples (N1-3), and 32 chemo-radiation resistant samples (RCRT), were included. newlineThe expression of CD44 standard (CD44s), variants (CD44v4, CD44v6), ALDH- newline1A1/3A1, Nanog, ERK1/2, GSK3and#946;, NICD (Notch), mTOR/PI3K, different TFs newline(interacting with Nanog promoter), the cell viability; and the MMP-9/-2 activity newlinewere assessed using RT-PCR, immunohistochemistry, Western blotting, ChIP newlineanalysis, MTT assay, and gelatin zymography. OSCC cell lines, including parental newlineSCC9/-4) and CisR-SCC9/-4 cells were used. Different molecules were controlled newlinewith knockdown of genes by siRNA (CD44v4/CD44v6, Nanog), specific SMI newline(PD98059/LY294002/Rapamycin inhibitors), and phytochemical treatment newline(epicatechin-3-gallate EGCG). Statistics were performed with Graphpadprism newlinesoftware (Prism 6.01) with the significance considered at pand#8804;0.05.