Abstract
Non-Hodgkin lymphoma (NHL) is one of the most common malignancies whose incidence increases, and the treatment results are not satisfactory. The aim of this study was to determine the capacity of NHL to produce MCP-1, chemokine that induces chemotaxis of macrophages and lymphoid cells. The mRNA expression and protein MCP-1 expression were determined in the samples of 20 patients with NHL and 8 reactive tonsils. MCP-1 mRNA was detected in 8/8 tonsils and in 19/20 patients with NHL by real-time PCR analysis. In addition, the amount of detected MCP-1 cDNA was significantly higher in patients with limited stage, good IPI, normal level of fibrinogen and LDH. Finally, in patients with aggressive NHL, the level of MCP-1 cDNA was higher than in indolent tumours. Immunohistochemical analysis revealed that majority of stromal elements such as macrophages, endothelial and smooth muscle cells in reactive as well as in neoplastic lymphoid tissue showed strong cytoplasmic MCP-1 expression. Moderate cytoplasmic MCP-1 expression was also observed in reactive lymphocytes, while tumour cells of indolent NHL were mostly pale in comparison with aggressive lymphomas which predominantly demonstrated intense MCP-1 staining. These intriguing preliminary results emphasize the need for further investigations that must be conducted on the representative sample with concordant measurement of serum MCP-1 level.
Similar content being viewed by others
References
Uppenkamp M, Feller AC (2002) Classification of malignant lymphoma. Onkologie 25:563–570
McLaughlin P (2002) Progress and promise in the treatment of indolent lymphomas. Oncologist 7:217–225
Grillo-Lopez AJ (2002) Zevalin: the first radioimmunotherapy approved for the treatment of lymphoma. Expert Rev Anticancer Ther 2:485–493
Coiffier B (2003) Immunochemotherapy: the new standard in aggressive non-Hodgkin’s lymphoma in the elderly. Semin Oncol 30(Suppl 2):21–27
Kurzrock R (2001) Cytokine deregulation in cancer. Biomed Pharmacother 55:543–547
Preti HA, Cabanillas F, Talpaz M, Tucker SL, Segmour JF, Kurzrock R (1997) Prognostic value of serum IL-6 in diffuse large-cell lymphoma. Ann Intern Med 127:186–194
Seymour JF, Talpaz M, Cabanillas F, Wetzler M, Kurzrock R (1995) Serum interleukin-6 levels correlate with prognosis in diffuse large-cell lymphoma. J Clin Oncol 13:575–582
Fayad L, Cabanillas F, Talpaz M, McLaughlin P, Kurzrock R (1998) High serum interleukin-6 levels correlate with a shorter failure-free survival in indolent lymphoma. Leuk Lymphoma 30:563–571
Rollins BJ (1997) Chemokines. Blood 90:909–928
Laurence ADJ (2005) Location, movement and survival: the role of chemokines in haematopoiesis and malignancy. Br J Haematol 132:255–267
Myers SJ, Wong LM, Charo IF (1996) Signal transduction and ligand specificity of the human monocyte chemotactic protein-1 receptor in transfected embryonic kidney cells. J Biol Chem 270:5786–5792
Bernardini G, Ribatti D, Spinetti G, Morbidelli L, Ziche M, Santoni A, Capogrossi MC, Napolitano M (2002) Analysis of the role of chemokines in angiogenesis. J Immunol Methods 273:83–101
Vanderkerken K, Van de Broek I, Eizirik DL, Van Valckenborgh E, Asosingh K, Van Riet I, Van Camp B (2002) Monocyte chemoattractant protein-1 (MCP-1), secreted by bone marrow endothelial cells, induces chemoattraction of 5T33MM multiple myeloma cells. Clin Exp Metastasis 19:87–90
Johrer K, Janke K, Krugmann J, Fiegl M, Griel R (2004) Transendothelial migration of myeloma cells is increased by tumor necrosis factor (TNF)-alpha via TNF receptor 2 and autocrine up-regulation of MCP-1. Clin Cancer Res 15:1901–1910
Luciani MG, Stoppacciaro A, Peri G, Mantovani A, Ruco LP (1998) The monocyte chemotactic protein-1 (MCP-1) and interleukine 8 (IL-8) in Hodgkin’s disease and in solid tumors. Mol Pathol 51:273–276
Chan JK (2001) The new world health organization classification of lymphomas: the past, the present and the future. Hematol Oncol 19:129–150
Carbone PP, Kaplan HS, Mushoff K, Smithers DW, Tubiana M (1971) Report of the committee in Hodgkin’s disease staging classification. Cancer Res 31:1860–1861
Hermans J, Krol AD, van Groningen K, Kluin-Nelemans JC, Kramer MH, Noordijk EM, Ong F, Wijermans PW (1995) International prognostic index for aggressive non-Hodgkin’s lymphoma is valid for all malignancy grades. Blood 86:1460–1463
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP (1982) Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol 5:649–655
Duletic-Nacinovic A, Sever-Prebilic M, Stifter S, Jonjic N, Hasan M, Labar B (2006) Interleukin-6 in patients with aggressive and indolent non-Hodgkin’s lymphoma: a predictor of prognosis. Clin Oncol 18:367–368
Serebriakov NB, Novik AA, Shamanskü SV (1998) Diagnostic and prognostic value of interleukin-6 in malignant non Hodgkin’s lymphomas. Vestn Ross Akad Med Nauk 10:32–36
Yee CY, Biondi A, Wang XH, Iscove NN, deSousa J, Aarden LA, Wong GG, Clark SC, Messner HA (1989) A possible autocrine role of interleukin-6 in two lymphoma cell lines. Blood 74:798–804
Salcedo R, Ponce ML, Young HA, Wasserman K, Ward JM, Kleinman HK, Oppenheim JJ, Murphy WJ (2000) Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood 96:34–40
Hong KH, Jewon R, Han KH (2005) Monocyte chemoattractant protein-1 induced angiogenesis is mediated by vascular endothelial growth factor-A. Blood 105:1405–1407
Kim MY, Byeon CW, Hong KH, Han KH, Jeong S (2005) Inhibition of the angiogenesis by the MCP-1 (monocyte chemoattractant protein-1) binding peptide. FEBS Lett 579:1597–1601
Vacca A, Ribatti D, Ruco L, Giacchetta F, Nico B, Quondamatteo F, Ria R, Iurlaro M, Dammacco F (1999) Angiogenesis extent and macrophage density increase simultaneously with pathological progression in B-cell non-Hodgkin’s lymphomas. Br J Cancer 79:965–970
Tedla N, Palladinetti P, Wakefield D, Lloyd A (1999) Abundant expression of chemokines in malignant and infective human lymphadenopathies. Cytokine 11:531–540
Husson H, Carideo EG, Cardoso AA, Lugli SM, Neuberg D, Munoz O, de Leval L, Schultze J, Freedman AS (2001) MCP-1 modulates chemotaxis by follicular lymphoma cells. Br J Haematol 115:554–562
Trentin L, Cabrelle A, Facco M, Carollo D, Miorin M, Tosoni A, Pizzo P, Binotto G, Nicolardi L, Zambello R, Adami F, Agostini C, Semenzato G (2004) Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas. Blood 104:502–508
Acknowledgments
We thank our technicians Tanja Kovačević, Ozren Štanfel, Ankica Brajenić and Ivan Dašek for technical assistance. This work was supported by the Ministry of Science, Education and Sports of the Republic of Croatia (grant numbers 062-0620095-0082 and 062-0620095-0079).
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Valković, T., Duletić-Načinović, A., Štifter, S. et al. Macrophage chemotactic protein-1 mRNA levels in non-Hodgkin lymphoma. Clin Exp Med 10, 229–235 (2010). https://doi.org/10.1007/s10238-010-0093-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10238-010-0093-6