The Effect of Tumor Resection and Radiotherapy on the Expression of Stem Cell Markers (CD44 and CD133) in Patients with Squamous Cell Carcinoma
-
Ladan Paya
,
Ali Rafat
,
Mehdi Talebi
,
Amirala Aghbali
,
Nikzad Shahidi
,
Babak Nejati
,
Parya Emamverdizadeh
,
Hojjatollah Nozad Charoudeh
Abstract
Background: Head and Neck Squamous Cell Carcinomas (HNSCCs) are heterogeneous malignancies that comprise 90% of the head and neck cancers. HNSCCs originate from the mucosal lining epithelium of the upper aerodigestive tract. Cancer stem cells (CSCs) that generate HNSCCs with the CD44, CD133, and ALDH phenotype and are resistant to radiotherapy and chemotherapy. In the current, the quantitative alteration in CD44 and CD133 expression pre- and post-tumor resection and radiotherapy was evaluated in HNSCC patients. Moreover, the alterations in the expression of Bax, Bak, Bcl-2, ALDH, and PTEN genes were measured.
Materials and Methods: Flow cytometry was performed to evaluate the alterations in CD44 and CD133 surface markers pre- and posttumor resection and radiotherapy. Quantitative real-time RT-PCR (qRT-PCR) was conducted to investigate the mRNA expression levels of Bax, Bak, Bcl-2, ALDH, and PTEN.
Results: The results indicated that the cancer stem cell CD44 surface marker significantly decreased after tumor resection and radiotherapy in HNSCC cases, while the decrease was insignificant for CD133 marker expression. mRNA expression level of Bcl-2 and ALDH was increased, but Bax and Bak gene expressions were reduced significantly
Conclusion: The results also indicated that the expression of CD44 significantly decreased after tumor resection and radiotherapy. The upregulation of mRNA level of Bcl-2 and ALDH, and the downregulation of Bax and Bak gene expression were noted in these cases when compared to the healthy control group.
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31. Lin J, Guan Z, Wang C, et al. Inhibitor of Differentiation 1 Contributes to Head and Neck Squamous Cell Carcinoma Survival via the NF-κB/Survivin and Phosphoinositide 3-Kinase/Akt Signaling Pathways. Clin Cancer Res. 2010;16(1):77-87.
32. Carter RJ, Milani M, Butterworth M, et al. Exploring the potential of BH3 mimetic therapy in squamous cell carcinoma of the head and neck. Cell Death Dis. 2019;10(12):912.
33. Chrysovergis A, Papanikolaou VS, Tsiambas E, et al. Digital Analysis of BCL2 Expression in Laryngeal Squamous Cell Carcinoma. Anticancer Res. 2019;39(3):1253-1257.
34. García-Heredia JM, Carnero A. Role of Mitochondria in Cancer Stem Cell Resistance. Cells. 2020;9(7):1693.
2. Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers. 2020;6(1):92.
3. Peitzsch C, Nathansen J, Schniewind SI, et al. Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: Identification, Characterization and Clinical Implications. Cancers (Basel). 2019;11(5):616.
4. Castellsagué X, Alemany L, Quer M, et al. HPV involvement in head and neck cancers: comprehensive assessment of biomarkers in 3680 patients. J Nat Cancer Inst. 2016;108(6):djv403.
5. Mason H, DeRubeis MB, Burke N, et al. Symptom management during and after treatment with concurrent chemoradiotherapy for oropharyngeal cancer: A review of the literature and areas for future research. World J Clin Oncol. 2016;7(2):220-6.
6. Tinhofer I, Saki M, Niehr F, et al. Cancer stem cell characteristics of circulating tumor cells. Int J Radiat Biol. 2014;90(8):622-7.
7. Almeida LO, Guimarães DM, Squarize CH, et al. Profiling the behavior of distinct populations of head and neck cancer stem cells. Cancers (Basel). 2016;8(1):7.
8. Prince M, Sivanandan R, Kaczorowski A, et al. Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci U S A. 2007;104(3):973-8.
9. Wei XD, Zhou L, Cheng L, et al. In vivo investigation of CD133 as a putative marker of cancer stem cells in Hep‐2 cell line. Head Neck. 2009;31(1):94-101.
10. Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 2018;25(1):20.
11. Peitzsch C, Kurth I, Ebert N, et al. Cancer stem cells in radiation response: current views and future perspectives in radiation oncology. Int J Radiat Biol. 2019;95(7):900-911.
12. Krause M, Dubrovska A, Linge A, et al. Cancer stem cells: Radioresistance, prediction of radiotherapy outcome and specific targets for combined treatments. Adv Drug Deliv Rev. 2017;109:63-73.
13. Steinbichler TB, Savic D, Dudás J, et al. Cancer stem cells and their unique role in metastatic spread. Semin Cancer Biol; 2020, 60: 148-156.
14. Turley EA, Noble PW, Bourguignon LY. Signaling properties of hyaluronan receptors. J Biol Chem. 2002;277(7):4589-92.
15. Fulda S. Tumor resistance to apoptosis. Int J cancer. 2009;124(3):511-5.
16. Molinari F, Frattini M. Functions and regulation of the PTEN gene in colorectal cancer. Front Oncol. 2014;3:326.
17. Wang SJ, Bourguignon LY. Role of hyaluronan-mediated CD44 signaling in head and neck squamous cell carcinoma progression and chemoresistance. Am J Pathol. 2011;178(3):956-63.
18. Kokko LL, Hurme S, Maula SM, et al. Significance of site-specific prognosis of cancer stem cell marker CD44 in head and neck squamous-cell carcinoma. Oral Oncol. 2011;47(6):510-6.
19. Wu MJ, Jan CI, Tsay YG, et al. Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling. Mol Cancer. 2010;9:283.
20. Chen YC, Chen YW, Hsu HS, et al. Aldehyde dehydrogenase 1 is a putative marker for cancer stem cells in head and neck squamous cancer. Biochem Biophys Res Commun. 2009;385(3):307-13.
21. Clay MR, Tabor M, Owen JH, et al. Single‐marker identification of head and neck squamous cell carcinoma cancer stem cells with aldehyde dehydrogenase. Head Neck. 2010;32(9):1195-201.
22. Richard V, Pillai MR. The stem cell code in oral epithelial tumorigenesis:‘the cancer stem cell shift hypothesis’. Biochim Biophysi Acta. 2010;1806(2):146-62.
23. Leinung M, Ernst B, Döring C, et al. Expression of ALDH1A1 and CD44 in primary head and neck squamous cell carcinoma and their value for carcinogenesis, tumor progression and cancer stem cell identification. Oncol Lett. 2015;10(4):2289-94.
24. Bourguignon LY, Zhu H, Shao L, et al. CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration. J Biol Chem. 2000;275(3):1829-38.
25. Bourguignon LY, Zhu H, Shao L, et al. Ankyrin–Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration. J Cell Biol. 2000;150(1):177-91.
26. Perez A, Neskey DM, Wen J, et al. CD44 interacts with EGFR and promotes head and neck squamous cell carcinoma initiation and progression. Oral Oncol. 2013;49(4):306-13.
27. Okada H, Yoshida J, Sokabe M, et al. Suppression of CD44 expression decreases migration and invasion of human glioma cells. Int J cancer. 1996;66(2):255-60.
28. da Costa AABA, Costa FDA, Araújo DV, et al. The roles of PTEN, cMET, and p16 in resistance to cetuximab in head and neck squamous cell carcinoma. Med Oncol. 2018;36(1):8.
29. Squarize CH, Castilho RM, Abrahao AC, et al. PTEN deficiency contributes to the development and progression of head and neck cancer. Neoplasia. 2013;15(5):461-71.
30. Gupta V, Maurya MK, Agarwal P, et al. Expression of aldehyde dehydrogenase 1A1 in oral squamous cell carcinoma and its correlation with clinicopathological parameters. Natl J Maxillofac Surg. 2022;13(2):208-215.
31. Lin J, Guan Z, Wang C, et al. Inhibitor of Differentiation 1 Contributes to Head and Neck Squamous Cell Carcinoma Survival via the NF-κB/Survivin and Phosphoinositide 3-Kinase/Akt Signaling Pathways. Clin Cancer Res. 2010;16(1):77-87.
32. Carter RJ, Milani M, Butterworth M, et al. Exploring the potential of BH3 mimetic therapy in squamous cell carcinoma of the head and neck. Cell Death Dis. 2019;10(12):912.
33. Chrysovergis A, Papanikolaou VS, Tsiambas E, et al. Digital Analysis of BCL2 Expression in Laryngeal Squamous Cell Carcinoma. Anticancer Res. 2019;39(3):1253-1257.
34. García-Heredia JM, Carnero A. Role of Mitochondria in Cancer Stem Cell Resistance. Cells. 2020;9(7):1693.
| Files | ||
| Issue | Vol 18, No 1 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijhoscr.v18i1.14748 | |
| Keywords | ||
| Head and neck squamous cell carcinoma; Cancer stem cells; Therapy resistance | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Paya L, Rafat A, Talebi M, Aghbali A, Shahidi N, Nejati B, Emamverdizadeh P, Nozad Charoudeh H. The Effect of Tumor Resection and Radiotherapy on the Expression of Stem Cell Markers (CD44 and CD133) in Patients with Squamous Cell Carcinoma. Int J Hematol Oncol Stem Cell Res. 2024;18(1):92-99.
