Production of Interferon-Inducible Protein-10 and Its Role as an Autocrine Invasion Factor in Nasal Natural Killer/T-Cell Lymphoma Cells

Purpose: Nasal natural killer (NK)/T-cell lymphoma is associated with Epstein-Barr virus and has poor prognosis because of local invasion and/or multiple dissemination. Recently, the role of chemokines/chemokine receptors in tumor proliferation and invasion has been shown. In this study, we examined whether the specific chemokines were related to the tumor behaviors in nasal NK/T-cell lymphoma. Experimental Design: A chemokine protein array was used to examine specific chemokines produced by SNK-6 and SNT-8 (Epstein-Barr viruspositive nasal NK/T-cell lymphoma lines). The expression of interferon inducible protein 10 (IP-10) and the IP-10 receptor CXCR3 was investigated by ELISA and flow cytometry. Cell growth and invasion were assessed by the MTT and Matrigel invasion assays, respectively. Immunohistologic staining and ELISA were used to examine IP-10 expression in biopsies and sera from patients, respectively. Results: IP-10 was specifically produced by SNK-6 and SNT-8. Moreover, CXCR3 was expressed on the NK cell lines. Functionally, IP-10 did not affect cell proliferation but enhanced cell invasion. In biopsy samples, IP-10 and CXCR3 expressions were detected in the lymphoma cells. Serum IP-10 levels in the patients were much higher than those of healthy controls and the levels were decreased during the complete remission phase after treatments. Conclusions: These results suggest that IP-10 may play an important role in cell invasion in nasal NK/T-cell lymphoma through an autocrine mechanism. (Clin Cancer Res 2009;15(22):67719)

[1]  M. Takahara,et al.  Nasal natural killer (NK)/T-cell lymphoma: clinical, histological, virological, and genetic features , 2009, International Journal of Clinical Oncology.

[2]  I. Ernberg,et al.  Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells. , 2008, The American journal of pathology.

[3]  B. Shalmon,et al.  CXCL10 promotes invasion-related properties in human colorectal carcinoma cells. , 2007, Cancer research.

[4]  G. Klein,et al.  Concomitant increase of LMP1 and CD25 (IL‐2‐receptor α) expression induced by IL‐10 in the EBV‐positive NK lines SNK6 and KAI3 , 2006, International journal of cancer.

[5]  Masahiro Takigawa,et al.  Chemokine Receptor Expression in Cutaneous T cell and NK/T-cell Lymphomas: Immunohistochemical Staining and In Vitro Chemotactic Assay , 2006, The American journal of surgical pathology.

[6]  A. Laurence.  Location, movement and survival: the role of chemokines in haematopoiesis and malignancy , 2006, British journal of haematology.

[7]  M. Takahara,et al.  Expression of Interleukin-9 in Nasal Natural Killer/T-Cell Lymphoma Cell Lines and Patients , 2005, Clinical Cancer Research.

[8]  A. Krensky,et al.  Retracted: Transactivation of the CCL5/RANTES gene by Epstein‐Barr virus latent membrane protein 1 , 2005, International journal of cancer.

[9]  H. Tesch,et al.  The Epstein‐Barr virus oncoprotein latent membrane protein 1 induces expression of the chemokine IP‐10: Importance of mRNA half‐life regulation , 2005, International journal of cancer.

[10]  K. Karube,et al.  Classification of distinct subtypes of peripheral T-cell lymphoma unspecified, identified by chemokine and chemokine receptor expression: Analysis of prognosis. , 2004, International journal of oncology.

[11]  S. Iida,et al.  CXC Chemokine Receptor 3 and CC Chemokine Receptor 4 Expression in T-Cell and NK-Cell Lymphomas with Special Reference to Clinicopathological Significance for Peripheral T-Cell Lymphoma, Unspecified , 2004, Clinical Cancer Research.

[12]  T. Yoshizaki,et al.  Epstein‐Barr Virus (EBV) Latent Membrane Protein 1 Induces Interleukin‐8 through the Nuclear Factor‐κB Signaling Pathway in EBV‐Infected Nasopharyngeal Carcinoma Cell Line , 2004, The Laryngoscope.

[13]  K. Karube,et al.  Differential Chemokine, Chemokine Receptor and Cytokine Expression in Epstein-Barr Virus-associated Lymphoproliferative Diseases , 2003, Leukemia & lymphoma.

[14]  A. van den Berg,et al.  Chemokines, cytokines and their receptors in Hodgkin's lymphoma cell lines and tissues. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  K. Takada,et al.  Human B Cells Immortalized with Epstein-Barr Virus Upregulate CCR6 and CCR10 and Downregulate CXCR4 and CXCR5 , 2002, Journal of Virology.

[16]  L. Yao,et al.  Interleukin‐18 expression induced by Epstein‐Barr virus‐infected cells , 2001, Journal of leukocyte biology.

[17]  T. Sekine,et al.  Characterization of novel natural killer (NK)-cell and gammadelta T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus. , 2001, Blood.

[18]  Y. Matsuo,et al.  A novel natural killer cell line (KHYG-1) from a patient with aggressive natural killer cell leukemia carrying a p53 point mutation , 2000, Leukemia.

[19]  N. Harris,et al.  Interleukin-18, interferon-gamma, IP-10, and Mig expression in Epstein-Barr virus-induced infectious mononucleosis and posttransplant lymphoproliferative disease. , 1999, The American journal of pathology.

[20]  E. Jaffe,et al.  Differential chemokine expression in tissues involved by Hodgkin's disease: direct correlation of eotaxin expression and tissue eosinophilia. , 1999, Blood.

[21]  Morishima,et al.  Characterization of Epstein–Barr virus (EBV)‐infected natural killer (NK) cell proliferation in patients with severe mosquito allergy; establishment of an IL‐2‐dependent NK‐like cell line , 1999, Clinical and experimental immunology.

[22]  W. Gong,et al.  Chemokines and their role in tumor growth and metastasis. , 1998, Journal of immunological methods.

[23]  W. Wilson,et al.  The role of Mig, the monokine induced by interferon-gamma, and IP-10, the interferon-gamma-inducible protein-10, in tissue necrosis and vascular damage associated with Epstein-Barr virus-positive lymphoproliferative disease. , 1997, Blood.

[24]  J. Chen,et al.  Upregulation of tumor necrosis factor-alpha gene by Epstein-Barr virus and activation of macrophages in Epstein-Barr virus-infected T cells in the pathogenesis of hemophagocytic syndrome. , 1997, The Journal of clinical investigation.

[25]  M. Seto,et al.  Clinicopathologic study of nasal T/NK‐cell lymphoma among the Japanese , 1997, Pathology international.

[26]  T. Osato,et al.  Nasal T‐cell lymphoma causally associated with Epstein‐Barr virus: Clinicopathologic, phenotypic, and genotypic studies , 1996, Cancer.

[27]  P. Gaulard,et al.  CD5-CD56+ T-cell receptor silent peripheral T-cell lymphomas are natural killer cell lymphomas. , 1996, Blood.

[28]  D. Taub,et al.  Alpha and beta chemokines induce NK cell migration and enhance NK-mediated cytolysis. , 1995, Journal of immunology.

[29]  H Stein,et al.  A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. , 1994, Blood.

[30]  J. Gong,et al.  Characterization of a human cell line (NK-92) with phenotypical and functional characteristics of activated natural killer cells. , 1994, Leukemia.

[31]  D. Taub,et al.  Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells , 1993, The Journal of experimental medicine.

[32]  P. Gaulard,et al.  Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. , 1993, Blood.

[33]  T. Osato,et al.  Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma , 1990, The Lancet.

[34]  K. Aozasa,et al.  Nation‐wide study of lethal mid‐line granuloma in Japan: Frequencies of Wegener's granulomatosis, polymorphic reticulosis, malignant lymphoma and other related conditions , 1989, International journal of cancer.

[35]  J. Ravetch,et al.  Biochemical characterization of a gamma interferon-inducible cytokine (IP-10) , 1987, The Journal of experimental medicine.

[36]  Y Iwamoto,et al.  A rapid in vitro assay for quantitating the invasive potential of tumor cells. , 1987, Cancer research.

[37]  F. Shido,et al.  Non‐Hodgkin's lymphoma of Waldeyer's ring and nasal cavity. Clinical and immunologic aspects , 1985, Cancer.

[38]  Andrew D. Luster,et al.  γ-Interferon transcriptionally regulates an early-response gene containing homology to platelet proteins , 1985, Nature.

[39]  M. Epstein,et al.  Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji). , 1966, Journal of the National Cancer Institute.

[40]  K. D. Devine,et al.  Primary lymphoma of the nose including a relationship to lethal midline granuloma. , 1966, American journal of surgery.

[41]  Walker Wg,et al.  Lethal midline granuloma (granuloma gangraenescens) at autopsy; report of a case and review of literature. , 1956 .

[42]  S. Colla,et al.  CXCR3 and its binding chemokines in myeloma cells: expression of isoforms and potential relationships with myeloma cell proliferation and survival. , 2006, Haematologica.

[43]  B. A. D. Luster.  BIOCHEMICAL CHARACTERIZATION OF A y INTERFERON-INDUCIBLE CYTOKINE (IP-10) , 2003 .

[44]  Clara D. Bloomfield,et al.  The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting--Airlie House, Virginia, November, 1997. , 2000, The hematology journal : the official journal of the European Haematology Association.

[45]  M. Hareyama,et al.  Prognostic factors and treatment outcome in non-Hodgkin's lymphoma of Waldeyer's ring. , 1997, Acta oncologica.

[46]  E. Jaffe,et al.  Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. , 1996, The American journal of surgical pathology.

[47]  G. Klein,et al.  Clonality, expression and methylation patterns of the Epstein-Barr virus genomes in lethal midline granulomas classified as peripheral angiocentric T cell lymphomas. , 1994, The Journal of general virology.

[48]  W. G. Walker,et al.  Lethal midline granuloma (granuloma gangraenescens) at autopsy; report of a case and review of literature. , 1956, Bulletin of the Johns Hopkins Hospital.