Proteomics Study of Mesenchymal Stem Cell-Like Cells Obtained from Tumor Microenvironment of Patients with Malignant and Benign Salivary Gland Tumors

Document Type : Original Article

Authors

1 Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Otolaryngology Research Center, Department of Otolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Pathology, Khalili Hospital, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Objective: Salivary gland tumors (SGTs) show some aggressive and peculiar clinicopathological behaviors that might 
be related to the components of the tumor microenvironment, especially mesenchymal stem cells (MSCs)-associated 
proteins. However, the role of MSCs-related proteins in SGTs tumorigenesis is poorly understood. This study aimed to 
isolate and characterize MSCs from malignant and benign tumor tissues and to identify differentially expressed proteins 
between these two types of MSCs. 
Materials and Methods: In this experimental study, MSC-like cells derived from benign (pleomorphic adenoma, n=5) and malignant (mucoepidermoid carcinoma, n=5) tumor tissues were verified by fluorochrome antibodies and flow cytometric analysis. Differentially expressed proteins were identified using two-dimensional polyacrylamide gel electrophoresis (2DE) and Mass spectrometry. 
Results: Results showed that isolated cells strongly expressed characteristic MSCs markers such as CD44, CD73, CD90, CD105, and CD166, but they did not express or weakly expressed CD14, CD34, CD45 markers. Furthermore, the expression of CD24 and CD133 was absent or near absent in both isolated cells. Results also discovered overexpression of Annexin A4 (Anxa4), elongation factor 1-delta (EF1-D), FK506 binding protein 9 (FKBP9), cytosolic platelet-activating factor acetylhydrolase type IB subunit beta (PAFAH1B), type II transglutaminase (TG2), and s-formylglutathione hydrolase (FGH) in MSCs isolated from the malignant tissues. Additionally, heat shock protein 70 (Hsp70), as well as keratin, type II cytoskeletal 7 (CK-7), were found to be overexpressed in MSCs derived from the benign ones. 
Conclusion: Malignant and benign SGTs probably exhibit a distinct pattern of tissue proteins that are most likely related to the metabolic pathway. However, further studies in a large number of patients are required to determine the applicability of identified proteins as new targets for cancer therapy. 

Keywords

References

  1. Dulguerov P, Todic J, Pusztaszeri M, Alotaibi NH. Why do parotid pleomorphic adenomas recur? A systematic review of pathological and surgical variables. Front Surg. 2017; 4: 26.
  2. Adelstein DJ, Koyfman SA, El-Naggar AK, Hanna EY. Biology and management of salivary gland cancers. Semin Radiat Oncol. 2012; 22(3): 245-253.
  3. Lanzel E, Robinson RA, Zimmerman MB, Pourian A, Hellstein JW. The use of immunohistochemistry in detection of perineural invasion in mucoepidermoid carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016; 121(6): 636-642.
  4. Alame M, Cornillot E, Cacheux V, Tosato G, Four M, De Oliveira L, et al. The molecular landscape and microenvironment of salivary duct carcinoma reveal new therapeutic opportunities. Theranostics. 2020; 10(10): 4383-4394.
  5. Baghban R, Roshangar L, Jahanban-Esfahlan R, Seidi K, Ebrahimi- Kalan A, Jaymand M, et al. Tumor microenvironment complexity and therapeutic implications at a glance. Cell Commun Signal. 2020; 18(1): 59.
  6. Ma H, Zhang M, Qin J. Probing the role of mesenchymal stem cells in salivary gland cancer on biomimetic microdevices. Integr Biol (Camb). 2012; 4(5): 522-530.
  7. Ghaderi A, Abtahi S. Mesenchymal stem cells: miraculous healers or dormant killers? Stem Cell Rev Rep. 2018; 14(5): 722- 733.
  8. Norozi F, Ahmadzadeh A, Shahrabi S, Vosoughi T, Saki N. Mesenchymal stem cells as a double-edged sword in suppression or progression of solid tumor cells. Tumour Biol. 2016; 37(9): 11679-11689.
  9. Razmkhah M, Abtahi S, Ghaderi A. Mesenchymal stem cells, immune cells and tumor cells crosstalk: a sinister triangle in the tumor microenvironment. Curr Stem Cell Res Ther. 2019; 14(1): 43-51.
  10. Bonuccelli G, Avnet S, Grisendi G, Salerno M, Granchi D, Dominici M, et al. Role of mesenchymal stem cells in osteosarcoma and metabolic reprogramming of tumor cells. Oncotarget. 2014; 5(17): 7575-7588.
  11. Alharbi RA. Proteomics approach and techniques in identification of reliable biomarkers for diseases. Saudi J Biol Sci. 2020; 27(3): 968-974.
  12. Saffarian A, Tarokh A, Reza Haghshenas M, Taghipour M, Chenari N, Ghaderi A, et al. Proteomics study of mesenchymal stem cell-like cells isolated from cerebrospinal fluid of patients with meningioma. Curr Proteomics. 2019; 16(4): 282-288.
  13. Taghipour M, Omidvar A, Razmkhah M, Ghaderi A, Mojtahedi Z. Comparative proteomic analysis of tumor mesenchymal-like stem cells derived from high grade versus low grade gliomas. Cell J. 2017; 19(2): 250-258.
  14. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-254.
  15. Elahi KC, Klein G, Avci-Adali M, Sievert KD, MacNeil S, Aicher WK. Human mesenchymal stromal cells from different sources diverge in their expression of cell surface proteins and display distinct differentiation patterns. Stem Cells Int. 2016; 2016: 5646384.
  16. Bourin P, Bunnell BA, Casteilla L, Dominici M, Katz AJ, March KL, et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the international federation for adipose therapeutics and science (IFATS) and the international society for cellular therapy (ISCT). Cytotherapy. 2013; 15(6): 641-648.
  17. Fang X, Zheng P, Tang J, Liu Y. CD24: from A to Z. Cell Mol Immunol. 2010; 7(2): 100-103.
  18. Chitteti BR, Kobayashi M, Cheng Y, Zhang H, Poteat BA, Broxmeyer HE, et al. CD166 regulates human and murine hematopoietic stem cells and the hematopoietic niche. Blood. 2014; 124(4): 519-529.
  19. Liou GY. CD133 as a regulator of cancer metastasis through the cancer stem cells. Int J Biochem Cell Biol. 2019; 106: 1-7.
  20. Sai B, Dai Y, Fan S, Wang F, Wang L, Li Z, et al. Cancer-educated mesenchymal stem cells promote the survival of cancer cells at primary and distant metastatic sites via the expansion of bone marrow-derived-PMN-MDSCs. Cell Death Dis. 2019; 10(12): 941.
  21. Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011; 121(10): 3804-3809.
  22. Boja ES, Rodriguez H. Proteogenomic convergence for understanding cancer pathways and networks. Clin Proteomics. 2014; 11(1): 22.
  23. Yarbrough WG, Slebos RJ, Liebler D. Proteomics: clinical applications for head and neck squamous cell carcinoma. Head Neck. 2006; 28(6): 549-558.
  24. Donadio E, Giusti L, Seccia V, Ciregia F, da Valle Y, Dallan I, et al. New insight into benign tumours of major salivary glands by proteomic approach. PLoS One. 2013; 8(8): e71874.
  25. Seccia V, Navari E, Donadio E, Boldrini C, Ciregia F, Ronci M, et al. Proteomic investigation of malignant major salivary gland tumors. Head Neck Pathol. 2020; 14(2): 362-373.
  26. Pavlova NN, Thompson CB. The emerging hallmarks of cancer metabolism. Cell Metab. 2016; 23(1): 27-47.
  27. Ngoi NYL, Eu JQ, Hirpara J, Wang L, Lim JSJ, Lee SC, Lim YC, et al. Targeting cell metabolism as cancer therapy. Antioxid Redox Signal. 2020; 32(5): 285-308.
  28. Mulvihill MM, Benjamin DI, Ji X, Le Scolan E, Louie SM, Shieh A, et al. Metabolic profiling reveals PAFAH1B3 as a critical driver of breast cancer pathogenicity. Chem Biol. 2014; 21(7): 831-840.
  29. DeBerardinis RJ, Chandel NS. Fundamentals of cancer metabolism. Sci Adv. 2016; 2(5): e1600200.
  30. Wiedl T, Arni S, Roschitzki B, Grossmann J, Collaud S, Soltermann A, et al. Activity-based proteomics: identification of ABHD11 and ESD activities as potential biomarkers for human lung adenocarcinoma. J Proteomics. 2011; 74(10): 1884-1894.
  31. Kumar S, Donti TR, Agnihotri N, Mehta K. Transglutaminase 2 reprogramming of glucose metabolism in mammary epithelial cells via activation of inflammatory signaling pathways. Int J Cancer. 2014; 134(12): 2798-2807.
  32. Li B, Tian XB, Hu RY, Xu FB, Zhao JM. Mechanism of BMP and TG2 in mesenchymal stem cell osteogenesis. Eur Rev MedPharmacol Sci. 2015; 19(22): 4214-4219.
  33. Niger C, Beazley KE, Nurminskaya M. Induction of chondrogenic differentiation in mesenchymal stem cells by TGF-beta cross-linked to collagen-PLLA [poly (L-lactic acid)] scaffold by transglutaminase 2. Biotechnol Lett. 2013; 35(12): 2193-2199.
  34. Zhou XZ, Lu KP. The isomerase PIN1 controls numerous cancer- driving pathways and is a unique drug target. Nat Rev Cancer. 2016; 16(7): 463-478.
  35. Lu Z, Hunter T. Prolyl isomerase Pin1 in cancer. Cell Res. 2014; 24(9): 1033-1049.
  36. Hassan MK, Kumar D, Naik M, Dixit M. The expression profile and prognostic significance of eukaryotic translation elongation factors in different cancers. PLoS One. 2018; 13(1): e0191377.
  37. Wei B, Guo C, Liu S, Sun MZ. Annexin A4 and cancer. Clin Chim Acta. 2015; 447: 72-78.
  38. Meer S, Altini M. CK7+/CK20- immunoexpression profile is typical of salivary gland neoplasia. Histopathology. 2007; 51(1): 26-32.
  39. Elmallah MIY, Cordonnier M, Vautrot V, Chanteloup G, Garrido C, Gobbo J. Membrane-anchored heat-shock protein 70 (Hsp70) in cancer. Cancer Lett. 2020; 469: 134-141.
  40. Chang W, Song BW, Lim S, Song H, Shim CY, Cha MJ, et al. Mesenchymal stem cells pretreated with delivered Hph-1- Hsp70 protein are protected from hypoxia-mediated cell death and rescue heart functions from myocardial injury. Stem Cells. 2009; 27(9): 2283-2292.
Cell Journal (Yakhteh)
Volume 24, Issue 4
April 2022
Pages 196-203

Files

Share

How to cite

Statistics