open access

Vol 2, No 2 (2017)
Original article
Published online: 2017-11-21
Get Citation

Metallothionein immunoreactivity profile in B-cell lymphomas of the palatine tonsils

Magdalena Dutsch-Wicherek1, Romana Tomaszewska2, Agata Lazar2, Konrad Dziobek3, Przemko Kwinta45, Łukasz Wicherek36
·
Medical Research Journal 2017;2(2):37-45.
Affiliations
  1. Department of Paediatric Otolaryngology, Chair of Paediatrics, Jagiellonian University Medical College, Kraków, Poland
  2. Uniwersytet Jagielloński Collegium Medicum Katedra Patomorfologii, Grzegórzecka 16, 31-531 Kraków
  3. Centrum Onkologii w Bydgoszczy, Romanowskiej 2, 85-796 Bydgoszcz
  4. Uniwersytet Jagielloński Collegium Medicum Uniwersytecki Szpital Dziecięcy, Wielicka 265, 30-663 Kraków
  5. Department of Pediatrics, Chair of Pediatrics, Jagiellonian Univeristy Medical College, Krakow, Poland
  6. Katedra i Klinika Onkologii, Radioterapii i Ginekologii Onkologicznej CM UMK

open access

Vol 2, No 2 (2017)
ORIGINAL ARTICLES
Published online: 2017-11-21

Abstract

Introduction. Tumours stimulate the remodelling of their microenvironment for their own survival. To protect their own growth and induce angiogenesis, tumours change the structure of the extracellular matrix and alter the function of existing as well as chemo-attracting immune system cells. MT is an anti-apoptotic and pro-proliferative protein that is also responsible for modulating the response of immune system cells. The expression of this protein by the fibroblasts of the tumour microenvironment is probably related to the remodelled phenotype of these cells by tumour influence on cancer-associated fibroblasts. Vimentin is a protein that appears to be the marker for the mesenchymal transition of cells from the epithelial phenotype. These cells seem to acquire the mesenchymal phenotype so that they can migrate and facilitate the development of metastases. Interestingly, the expression of vimentin has also been observed in the tumour microenvironment and may serve as a marker of a remodelled stroma in the process of facilitating tumour spread. Materials and methods. We recruited 25 patients with tonsillar DLBCL (diffuse large B-cell lymphoma) and tonsillar DLBCL with cervical lymph node involvement (i.e. stages I and II of the disease) and analysed tissue samples from the lymphoma and tumour microenvironment of each. We also analysed the immunoreactivity levels of the following antigens in the palatine tonsil lymphoma and its stroma: MT, vimentin, and CD56- and CD57-positive cells. Results. A statistically significantly higher MT and vimentin immunoreactivity was observed in the lymphoma as compared to the stroma tissue samples. However, both MT-positive fibroblasts and MT-positive macrophages were observed in the stroma. Additionally, statistically significantly lower numbers of CD56- and CD57-positive cells were identified in the lymphoma and the stroma samples than in the reference group samples. Conclusions. The high vimentin immunoreactivity in the tumour and its stroma, together with MT-expressing fibroblasts and macrophages, as well as a CD56- and CD57-positive cell deficit, would seem to confirm microenvironment remodelling and the participation of MT in tumour remodelling.

Abstract

Introduction. Tumours stimulate the remodelling of their microenvironment for their own survival. To protect their own growth and induce angiogenesis, tumours change the structure of the extracellular matrix and alter the function of existing as well as chemo-attracting immune system cells. MT is an anti-apoptotic and pro-proliferative protein that is also responsible for modulating the response of immune system cells. The expression of this protein by the fibroblasts of the tumour microenvironment is probably related to the remodelled phenotype of these cells by tumour influence on cancer-associated fibroblasts. Vimentin is a protein that appears to be the marker for the mesenchymal transition of cells from the epithelial phenotype. These cells seem to acquire the mesenchymal phenotype so that they can migrate and facilitate the development of metastases. Interestingly, the expression of vimentin has also been observed in the tumour microenvironment and may serve as a marker of a remodelled stroma in the process of facilitating tumour spread. Materials and methods. We recruited 25 patients with tonsillar DLBCL (diffuse large B-cell lymphoma) and tonsillar DLBCL with cervical lymph node involvement (i.e. stages I and II of the disease) and analysed tissue samples from the lymphoma and tumour microenvironment of each. We also analysed the immunoreactivity levels of the following antigens in the palatine tonsil lymphoma and its stroma: MT, vimentin, and CD56- and CD57-positive cells. Results. A statistically significantly higher MT and vimentin immunoreactivity was observed in the lymphoma as compared to the stroma tissue samples. However, both MT-positive fibroblasts and MT-positive macrophages were observed in the stroma. Additionally, statistically significantly lower numbers of CD56- and CD57-positive cells were identified in the lymphoma and the stroma samples than in the reference group samples. Conclusions. The high vimentin immunoreactivity in the tumour and its stroma, together with MT-expressing fibroblasts and macrophages, as well as a CD56- and CD57-positive cell deficit, would seem to confirm microenvironment remodelling and the participation of MT in tumour remodelling.
Get Citation

Keywords

MT, tumour microenvironment, vimentin, tumour-associated macrophages, cancer-associated fibroblasts, EMT

About this article
Title

Metallothionein immunoreactivity profile in B-cell lymphomas of the palatine tonsils

Journal

Medical Research Journal

Issue

Vol 2, No 2 (2017)

Article type

Original article

Pages

37-45

Published online

2017-11-21

Page views

786

Article views/downloads

768

DOI

10.5603/MRJ.2017.0007

Bibliographic record

Medical Research Journal 2017;2(2):37-45.

Keywords

MT
tumour microenvironment
vimentin
tumour-associated macrophages
cancer-associated fibroblasts
EMT

Authors

Magdalena Dutsch-Wicherek
Romana Tomaszewska
Agata Lazar
Konrad Dziobek
Przemko Kwinta
Łukasz Wicherek

References (42)
  1. Doll DC. Introduction: extranodal lymphomas. Semin Oncol. 1999; 26: 249–250.
  2. Jacobs C, Hoppe RT. Non-Hodgkin's lymphomas of head and neck extranodal sites. Int J Radiat Oncol Biol Phys. 1985; 11(2): 357–364.
  3. Jacobs C, Weiss L, Hoppe RT. The management of extranodal head and neck lymphomas. Arch Otolaryngol Head Neck Surg. 1986; 112(6): 654–658.
  4. Banfi A, Bonadonna G, Carnevali G, et al. Lymphoreticular sarcomas with primary involvement of Waldeyer's ring. Clinical evaluation of 225 cases. Cancer. 1970; 26(2): 341–351.
  5. Avilés A, Delgado S, Ruiz H, et al. Hodgkin’s and non-Hodgkin’s lymphoma. Eur J Cancer B Oral Oncol. 1996; 32B: 19–23.
  6. Harabuchi Y, Tsubota H, Ohguro S, et al. Prognostic factors and treatment outcome in non-Hodgkin's lymphoma of Waldeyer's ring. Acta Oncol. 1997; 36(4): 413–420.
  7. Yamanaka N, Harabuchi Y, Sambe S, et al. Non-Hodgkin's lymphoma of Waldeyer's ring and nasal cavity. Clinical and immunologic aspects. Cancer. 1985; 56(4): 768–776.
  8. Cherian MG, Jayasurya A, Bay BH. Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat Res. 2003; 533(1-2): 201–209.
  9. Kagi JH, Scheffer A. of metallothionein. Biochemistry of metallothionein Biochemistry. 2003; 27: 8509–8515.
  10. Cherian MG, Apostolova MD. Nuclear localization of metallothionein during cell proliferation and differentiation. Cell Mol Biol (Noisy-le-grand). 2000; 46(2): 347–356.
  11. Fan LZ, Cherian MG. Potential role of p53 on metallothionein induction in human epithelial breast cancer cells. Br J Cancer. 2002; 87(9): 1019–1026.
  12. Werynska B, Pula B, Kobierzycki C, et al. Metallothioneins in the lung cancer. Folia Histochemica et Cytobiologica. 2015; 53(1): 1–10.
  13. Dutsch-Wicherek M, Popiela TJ, Klimek M, et al. Metallothionein stroma reaction in tumor adjacent healthy tissue in head and neck squamous cell carcinoma and breast adenocarcinoma. Neuro Endocrinol Lett. 2005; 26(5): 567–574.
  14. Dutsch-Wicherek M, Sikora J, Tomaszewska R. The possible biological role of metallothionein in apoptosis. Front Biosci. 2008; 13: 4029–4038.
  15. Hellquist HB. Apoptosis in epithelial hyperplastic laryngeal lesions. Acta Otolaryngol Suppl. 1997; 527: 25–29.
  16. Muramatsu Y, Hasegawa Y, Fukano H, et al. Metallothionein immunoreactivity in head and neck carcinomas; special reference to clinical behaviors and chemotherapy responses. Anticancer Res. 2000; 20(1A): 257–264.
  17. Sundelin K, Jadner M, Norberg-Spaak L, et al. Metallothionein and Fas (CD95) are expressed in squamous cell carcinoma of the tongue. Eur J Cancer. 1997; 33(11): 1860–1864.
  18. Theocharis SE, Margeli AP, Klijanienko JT, et al. Metallothionein expression in human neoplasia. Histopathology. 2004; 45(2): 103–118.
  19. Popiela TJ, Rudnicka-Sosin L, Dutsch-Wicherek M, et al. The metallothionein and RCAS1 expression analysis in breast cancer and adjacent tissue regarding the immune cells presence and their activity. Neuro Endocrinol Lett. 2006; 27(6): 786–794.
  20. Popiela TJ, Klimek M, Wicherek L, et al. The characterization of the exposure to immune mediated apoptosis and the regulation of immune cytotoxic activity in the environment of a neoplasm and in decidua. Neuro Endocrinol Lett. 2006; 27(6): 779–785.
  21. Witz I. The Tumor Microenvironment: The Making of a Paradigm. Cancer Microenvironment. 2009; 2(S1): 9–17.
  22. Dutsch-Wicherek M, Lazar A, Tomaszewska R. The potential role of mt and vimentin immunoreactivity in the remodeling of the microenvironment of parotid adenocarcinoma. Cancer Microenviron. 2010; 4(1): 105–113.
  23. Dutsch-Wicherek M, Lazar A, Tomaszewska R, et al. Analysis of metallothionein and vimentin immunoreactivity in pharyngeal squamous cell carcinoma and its microenvironment. Cell Tissue Res. 2013; 352(2): 341–349.
  24. Dutsch-Wicherek M, Tomaszewska R, Lazar A, et al. The evaluation of metallothionein expression in nasal polyps with respect to immune cell presence and activity. BMC Immunol. 2010; 11: 10.
  25. Walentowicz-Sadlecka M, Koper A, Krystyna G, et al. The analysis of metallothionein immunoreactivity in stromal fibroblasts and macrophages in cases of uterine cervical carcinoma with respect to both the local and distant spread of the disease. Am J Reprod Immunol. 2013; 70(3): 253–261.
  26. Kazmierczak W, Lazar A, Tomaszewska R, et al. Analysis of the intensity of immune cell infiltration and immunoreactivity of RCAS1 in diffuse large B-cell lymphoma of the palatine tonsil and its microenvironment. Cell Tissue Res. 2015; 361(3): 823–831.
  27. Franke WW, Grund C, Kuhn C, et al. Formation of cytoskeletal elements during mouse embryogenesis. III. Primary mesenchymal cells and the first appearance of vimentin filaments. Differentiation. 1982; 23(1): 43–59.
  28. Larsson A, Wilhelmsson U, Pekna M, et al. Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(-/-)Vim(-/-) mice. Neurochem Res. 2004; 29(11): 2069–2073.
  29. Cochard P, Paulin D. Initial expression of neurofilaments and vimentin in the central and peripheral nervous system of the mouse embryo in vivo. J Neurosci. 1984; 4(8): 2080–2094.
  30. de Souza PC, Katz SG. Coexpression of cytokeratin and vimentin in mice trophoblastic giant cells. Tissue Cell. 2001; 33(1): 40–45.
  31. Ko SH, Suh SH, Kim BJ, et al. Expression of the intermediate filament vimentin in proliferating duct cells as a marker of pancreatic precursor cells. Pancreas. 2004; 28(2): 121–128.
  32. Mahrle G, Bolling R, Osborn M, et al. Intermediate filaments of the vimentin and prekeratin type in human epidermis. J Invest Dermatol. 1983; 81(1): 46–48.
  33. Carter V, Shenton BK, Jaques B, et al. Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation. Transplant Proc. 2005; 37(2): 654–657.
  34. Evans RM. Vimentin: the conundrum of the intermediate filament gene family. Bioessays. 1998; 20(1): 79–86.
  35. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer. 2002; 2(6): 442–454.
  36. Chaffer CL, Brennan JP, Slavin JL, et al. Mesenchymal-to-epithelial transition facilitates bladder cancer metastasis: role of fibroblast growth factor receptor-2. Cancer Res. 2006; 66(23): 11271–11278.
  37. Satelli A, Li S. Vimentin in cancer and its potential as a molecular target for cancer therapy. Cell Mol Life Sci. 2011; 68(18): 3033–3046.
  38. Imoto A, Okada M, Okazaki T, et al. Metallothionein-1 isoforms and vimentin are direct PU.1 downstream target genes in leukemia cells. J Biol Chem. 2010; 285(14): 10300–10309.
  39. Poulsen CB, Borup R, Borregaard N, et al. Prognostic significance of metallothionein in B-cell lymphomas. Blood. 2006; 108(10): 3514–3519.
  40. Mantovani A, Allavena P, Sica A, et al. Cancer-related inflammation. Nature. 2008; 454(7203): 436–444.
  41. Hugo H, Ackland ML, Blick T, et al. Epithelial--mesenchymal and mesenchymal--epithelial transitions in carcinoma progression. J Cell Physiol. 2007; 213(2): 374–383.
  42. Grünert S, Jechlinger M, Beug H. Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis. Nat Rev Mol Cell Biol. 2003; 4(8): 657–665.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk, Poland
tel.:+48 58 320 94 94, fax:+48 58 320 94 60, e-mail: viamedica@viamedica.pl