alexa Acquisition of Cancer Stem Cell Behaviour Plays a Role in Drug Resistance to Combination Chemotherapy and Prognosis in Head and Neck Cancer | OMICS International | Abstract
ISSN: 2157-7633

Journal of Stem Cell Research & Therapy
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Research Article

Acquisition of Cancer Stem Cell Behaviour Plays a Role in Drug Resistance to Combination Chemotherapy and Prognosis in Head and Neck Cancer

Sindhu Govindan Valiyaveedan1,7, Balaji Ramachandran2, Jeyaram Iliaraja3, Ravindra DR1, Bonney Lee James1, Kulsum Safeena1, Ramanan Pandian4, Gangotri Siddappa1,7, Debashish Das5, Nisheena R6, Aravindakshan Jayaprakash2,Vikram Kekatpure7, Wesley Hicks Jr8,9, Moni A Kuriakose1,7,9 and Amritha Suresh1,7,9*

1DSRG-5, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Foundation, Bangalore, India

2Department of Pharmacology, Syngene International Pvt Ltd. Biocon, Bangalore, India

3Department of Clinical Research, Mazumdar Shaw Medical Center, Narayana Health, Bangalore, India

4GROW Laboratory, Narayana Nethralaya, Narayana Health City, Bangalore, India

5Stem Cell Research Laboratory, Narayana Nethralaya, Narayana Health City, Bangalore, India

6Department of Pathology, Mazumdar Shaw Medical Center, Narayana Health, Bangalore, India

7Department of Head and Neck Oncology, Mazumdar Shaw Medical Center, Narayana Health, Bangalore, India

8Department of Head and Neck/Plastic & Reconstructive Surgery, Roswell Park Cancer Institute, Elm Street, Buffalo, USA

9Mazumdar Shaw Medical Centre-Roswell Park Collaboration Program, Roswell Park Cancer Institute, Elm Street, Buffalo, USA

*Corresponding Author:
Dr. Amritha Suresh, PhD
Principal Investigator
DSRG- 5, Mazumdar Shaw
Centre for Translational Research (MSCTR)
8th Floor, 'A' Block, No. 258/A
NHPL Multi-Specialty and Oncology Hospital
Bommasandra Industrial Area
Anekal Taluk, Bangalore- 560099, India
Tel: +918105114670
E-mail: [email protected]

Received date: December 06, 2014; Accepted date: January 19, 2015; Published date: January 21, 2015

Citation: Valiyaveedan SG, Ramachandran B, Iliaraja J, Ravindra DR , James BL, et al. (2015) Acquisition of Cancer Stem Cell Behaviour Plays a Role in Drug Resistance to Combination Chemotherapy and Prognosis in Head and Neck Cancer. J Stem Cell Res Ther 5:261. doi:10.4172/2157-7633.1000261

Copyright: © 2015 Valiyaveedan SG, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: Head and Neck Squamous Cell Carcinoma (HNSCC) demonstrate an exceptional initial response to induction chemotherapy; nevertheless, loco-regional relapse is widespread and not clearly understood. In this study, we investigated the role of Cancer Stem Cells (CSCs) in mediating chemo resistance using patient cohorts and cell line models.
Methods: Profiling of CSC markers was carried out in primary untreated (Cohort I, N=33) and post treatment recurrent (Cohort II, N=27) HNSCC patients by Quantitative PCR (Q-PCR) and Immunihistochemistry (IHC). The prognostic significance of these markers was assessed by ROC curves and logistic regression analyses. The stem cell related behaviour of the drug resistant TPFR cell lines was assessed by the expression of CSC markers and other properties such as self-renewal, migration and tumorigenicity.
Results: Post-treatment recurrent patients showed an over-expression of CSC markers (CD44, ABCG2 and NOTCH1) compared to the treatment naïve cohort. Additionally, CD44 (p=0.028) and ABCG2 (p=0.019), in combination, were poor prognosticators (AUC 0.76). The resistant cell lines (Hep-2 TPFR and CAL-27 TPFR) were further characterized to delineate the role of CSCs in drug resistance. Analogous to the patients, these cells showed an enrichment of CD44+ cells accompanied by an increased spheroid formation (p<0.005) and migratory capacity (p<0.05). The up regulation of CSC markers (CD133, BMI and NOTCH1) and their resistance-mediating targets such as drug transporters and survival/anti-apoptotic pathways suggested possible causal mechanisms. Furthermore, the higher clonogenic survival in the presence of cisplatin (p<0.05) signifying an increased self-renewal capacity with drug resistance. The Hep-2 TPFR (102 cells) also showed an increased tumorigenicity (2/3; 9.5-fold increase in tumor burden) as compared to the parental (1/3; 6-fold).
Conclusion: Our findings suggest that TPF combination chemotherapy enriches the resident cache of CSCs, ultimately leading to drug resistance. Consequently, in a sub set of patients, these drug resistant CSCs might contribute towards disease relapse/recurrence.

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