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Effect of CXCL9-CXCR3 Cytokine Signaling Pathway in Polycytemia Vera

Year 2018, Volume: 8 Issue: 3, 84 - 92, 02.12.2018

Abstract

DOI:
10.26650/experimed.2019.18006


Objective: Myeloproliferative neoplasms
(MPNs) are among the most common myeloproliferative disorders. MPNs are
characterized by excessive production of terminally differentiated blood cells.
The expression of CXCR3, responsible for regulating the proliferation of
healthy hematopoietic stem cells, is known to be induced by
granulocyte-macrophage colony stimulating factor (GM-CSF). The aim of this
study is to investigate the role of CXCL9-CXCR3 signaling pathway in the
progression of MPN.



Material and Method: We determined the
expression of CXCL9 and two isoforms of the CXCR3 receptor (CXCR3A and CXCR3B)
on the surface of human peripheral blood mononuclear cells (PBMC) and cancer
stem cells. Real-time polymerase chain reaction (qPCR) was used to measure expression
levels, and flow cytometry was used to examine the presence of cell surface
receptors. In addition, qPCR was used to quantify CXCR3 expression after GM-CSF
application in cell culture. In PBMC and CD34+ cells, the mRNA level of CXCR3A
expression was found to be elevated in patients with MPN.



Results: There was no statistically
significant difference in mRNA expression of CXCR3B and CXCL9 between patients
and healthy controls.There was significant reduction in cell surface expression
of the CXCR3 receptor in PBMC obtained from patients. T



Conclusion: hus, these results indicate
that imbalance in the expression of CXCR3A/CXCR3B isoforms and chemokines
CXCL9, CXCL10 and CXCL11 that bind to these receptors, may mediate inflammation
and cancer progression in MPN.

References

  • 1. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937-51. 2. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood 2016: 127; 2391-405. 3. Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood 2017; 129: 667-79. 4. Geyer J, Orazi A. Myeloproliferative neoplasms (BCR‐ABL1 negative) and myelodysplastic/myeloproliferative neoplasms: current diagnostic principles and upcoming updates. Int J Lab Hematol 2016; 38: 12-9. 5. Kaplan JB, Stein BL, McMahon B, Giles FJ, Platanias LC. Evolving therapeutic strategies for the classic Philadelphia-negative myeloproliferative neoplasms. EBio Med 2016; 3: 17-25. 6. Geyer HL, Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? Blood 2014; 124: 3529-37. 7. Tefferi A. Mutations galore in myeloproliferative neoplasms: would the real Spartacus please stand up? : Nature Publishing Group; 2011. 8. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. New Eng J Med 2013; 369: 2379-90. 9. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. New Eng J Med 2013; 369: 2391-405. 10. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: e270. 11. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472-6. 12. Emanuel RM, Dueck AC, Geyer HL, Kiladjian J-J, Slot S, Zweegman S, et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 2012; 30: 4098. 13. Geyer HL, Scherber RM, Dueck AC, Kiladjian J-J, Xiao Z, Slot S, et al. Distinct clustering of symptomatic burden among myeloproliferative neoplasm patients: retrospective assessment in 1470 patients. Blood 2014; 123: 3803-10. 14. Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 2011; 29: 3179-84. 15. Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi A, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013; 27: 1874. 16. Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS-plus: DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 2011; 29: 392-7. 17. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 2010; 115: 1703-8. 18. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009; 113: 2895-901. 19. Kaifie A, Kirschner M, Wolf D, Maintz C, Hänel M, Gattermann N, et al. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol 2016; 9: 18. 20. Mesa R, Miller CB, Thyne M, Mangan J, Goldberger S, Fazal S, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and productivity: the MPN Landmark survey. BMC Cancer 2016; 16: 167. 21. Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 2011; 118: 401-8. 22. Johansson P, Mesa R, Scherber R, Abelsson J, Samuelsson J, Birgegård G, et al. Association between quality of life and clinical parameters in patients with myeloproliferative neoplasms. Leuk Lymphoma 2012; 53: 441-4. 23. Abelsson J, Andréasson B, Samuelsson J, Hultcrantz M, Ejerblad E, Johansson B, et al. Patients with polycythemia vera have worst impairment of quality of life among patients with newly diagnosed myeloproliferative neoplasms. Leuk Lymphoma 2013; 54: 2226-30. 25. Mesa RA, Niblack J, Wadleigh M, Verstovsek S, Camoriano J, Barnes S, ve ark. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs). Cancer 2007; 109: 68-76. 26. da Costa Cacemiro M, Cominal JG, Tognon R, de Souza Nunes N, Simões BP, de Figueiredo-Pontes LL, et al. Philadelphia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation. Hematol Transfus Cell Ther 2018. 27. Jinquan T, Quan S, Jacobi HH, Jing C, Millner A, Jensen B, et al. CXC chemokine receptor 3 expression on CD34+ hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor: chemotaxis and adhesion induced by its ligands, interferon γ-inducible protein 10 and monokine induced by interferon γ. Blood 2000; 96: 1230-8. 28. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 2001; 25: 402-8. 29. Callahan MK, Williams KA, Kivisäkk P, Pearce D, Stins MF, Ransohoff RM. CXCR3 marks CD4+ memory T lymphocytes that are competent to migrate across a human brain microvascular endothelial cell layer. J Neuroimmunol 2004; 153: 150-7. 30. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994; 76: 301-14. 31. Baggiolini M. Chemokines and leukocyte traffic. Nature 1998; 392: 565. 32. Glaser J, Gonzalez R, Perreau VM, Cotman CW, Keirstead HS. Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury. J Neurosci Res 2004; 77: 701-8. 33. Kelsen SG, Aksoy MO, Yang Y, Shahabuddin S, Litvin J, Safadi F, et al. The chemokine receptor CXCR3 and its splice variant are expressed in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2004; 287: L584-91. 34. Chakraborty K, Bose A, Pal S, Chattopadhyay U, Baral R. Interferon-α2b Restores the Impaired Chemotactic Activity of Peripheral Blood Mononuclear Cells from Head and Neck Squamous Cell Carcinoma Patients by Modulating CXC Receptor Ligand Interaction. J Interferon Cytokine Res 2007; 28: 487-500. 35. Chakraborty K, Bose A, Pal S, Sarkar K, Goswami S, Ghosh D, et al. Neem leaf glycoprotein restores the impaired chemotactic activity of peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients by maintaining CXCR3/CXCL10 balance. Int Immunopharmacol 2008; 8: 330-40. 36. Furuya M, Yoneyama T, Miyagi E, Tanaka R, Nagahama K, Miyagi Y, et al. Differential expression patterns of CXCR3 variants and corresponding CXC chemokines in clear cell ovarian cancers and endometriosis. Gynecol Oncol 2011; 122: 648-55. 37. Wu Q, Dhir R, Wells A. Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion. Mol Cancer 2012; 11: 3. 38. Datta D, Contreras AG, Grimm M, Waaga-Gasser AM, Briscoe DM, Pal S. Calcineurin inhibitors modulate CXCR3 splice variant expression and mediate renal cancer progression. J American Soc Nephrol 2008; 19: 2437-46. 39. Romagnani P, Beltrame C, Annunziato F, Lasagni L, Luconi M, Galli G, et al. Role for interactions between IP-10/Mig and CXCR3 in proliferative glomerulonephritis. J American Soc Nephrol 1999; 10: 2518-26. 40. Romagnani P, Lazzeri E, Lasagni L, Mavilia C, Beltrame C, Francalanci M, et al. IP-10 and Mig production by glomerular cells in human proliferative glomerulonephritis and regulation by nitric oxide. J American Soc Nephrol 2002; 13: 53-64. 41. Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res 2006; 4: 221-33. 42. Perwez Hussain S, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 2007; 121: 2373-80. 43. Maeda H, Akaike T. Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry 1998; 63: 854-65. 44. Ma B, Khazali A, Wells A. CXCR3 in carcinoma progression. Histol Histopathol 2015; 30: 781. 45. Lleo A, Zhang W, Zhao M, Tan Y, Bernuzzi F, Zhu B, et al. DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis. Clin Epigenetics 2015; 7: 61. 46. Kumar DSS, Wells A. CXCR3 epigenome switches splice variants in prostate cancer. AACR; 2013. 47. Urra S, Fischer MC, Martínez JR, Véliz L, Orellana P, Solar A, et al. Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis? Oncotarget 2018; 9: 2445. 48. Witte E, Kokolakis G, Witte K, Warszawska K, Friedrich M, Christou D, et al. Interleukin-29 induces epithelial production of CXCR3A ligands and T-cell infiltration. J Mol Med 2016; 94: 391-400. 49. Walters JH, Mc GI. The mechanism of malarial hepatomegaly and its relationship to hepatic fibrosis. Trans R Soc Trop Med Hyg 1960; 54: 135-45. 50. Van Raemdonck K, Van den Steen PE, Liekens S, Van Damme J, Struyf S. CXCR3 ligands in disease and therapy. Cytokine Growth Factor Rev 2015; 26: 311-27. 51. Wasmuth H, Weiskirchen R. Pathogenesis of liver fibrosis: modulation of stellate cells by chemokines. Zeitschrift fur Gastroenterologie 2010; 48: 38-45. 52. Li J, Liu B, Shi Y, Xie K-L, Yin H-F, Yan L-n, et al. CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction. J Immunol Res 2016; 2016: 9276986. 53. Baldi P, Long AD. A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics 2001; 17: 509-19. 54. Szallasi Z. Genetic network analysis in light of massively parallel biological data acquisition. Pac Symp Biocomput 1999; 5-16. 55. Colvin RA, Campanella GS, Sun J, Luster AD. Intracellular domains of CXCR3 that mediate CXCL9, CXCL10, and CXCL11 function. J Biol Chem 2004; 279: 30219-27. 56. Meiser A, Mueller A, Wise EL, McDonagh EM, Petit SJ, Saran N, ve ark. The chemokine receptor CXCR3 is degraded following internalization and is replenished at the cell surface by de novo synthesis of receptor. J Immunol 2008; 180: 6713-24. 57. Wu Q, Dhir R, Wells A. Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion. Mol Cancer 2012; 11: 3.

Polisitemia Vera’da CXCL9-CXCR3 Sitokin Sinyal Yolağının Etkisi

Year 2018, Volume: 8 Issue: 3, 84 - 92, 02.12.2018

Abstract

DOI:
10.26650/experimed.2019.18006


Amaç: Miyeloproliferatif Neoplaziler (MPN),
miyeloproliferatif bozukluklar arasında en sık görülen hastalıklardandır.
Tamamen işlevsel olan ve son aşamaya kadar farklılaşmış kan hücrelerinin aşırı
üretimi ile karakterize edilirler. Önceki çalışmalarda Granülosit-Makrofaj
Koloni Uyarıcı Faktörün (GM-CSF) sağlıklı hematopoietik kök hücreler (HKH)
de proliferasyon kontrolünden sorumlu CXCR3 ekspresyonunu arttırdığı
gösterilmiştir. Bu çalışmanın amacı, CXCL9-CXCR3 sinyal yolağının MPN
progresyonunda etkisinin araştırılmasıdır.

Gereç ve Yöntem: Çalışmada, MPN ve
sağlıklı  insan perifer kan mononükleer
hücrelerinde (MNH) ve kanser HKH de CXCL9 kemokini ve bunun reseptörü olan
CXCR3
ün iki izoformunun (CXCR3A ve CXCR3B) gen ifade seviyeleri, MNH
yüzeyinde ise CXCR3 reseptör varlığı incelenmiştir. Ekspresyon seviyelerini
araştırmak amacıyla kantitatif gerçek zamanlı polimeraz zincir reaksiyonu
(PZR), hücre yüzey reseptör durumunun incelenmesi içinse akım ölçer metotları
kullanılmıştır. GM-CSF
in MNH ve CD34+ hücrelerinde
uygulamasının ardından CXCR3 ekspresyonu değerlendirilmiştir.

Bulgular: MNHde
CXCR3A ifadesinin hastalarda sağlıklılara göre istatistiksel olarak anlamlı
arttığı bulunmuşur. Hasta ve sağlıklı kontrol grupları arasında CXCR3B ve CXCL9
ifade seviyeleri kıyaslandığında istatistiksel olarak anlamlı bir fark olmadığı
tespit edilmiştir. CXCR3 Hücre yüzey reseptör durumuna bakıldığında ise
hastalardan elde edilen MNH
deki anlatımda sağlıklı gruptan elde
edilenlere göre anlamlı bir azalma olduğu görülmüştür.







Sonuç: Bu sonuçlar MPNde
CXCR3A/CXCR3B dengesi ile bu reseptörlere özgün olarak bağlanan kemokinler
CXCL9, CXCL10 ve CXCL11
in inflamasyon ve kanser progresyonu
ile ilişkili olabileceğini düşündürmektedir.

References

  • 1. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114: 937-51. 2. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood 2016: 127; 2391-405. 3. Vainchenker W, Kralovics R. Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms. Blood 2017; 129: 667-79. 4. Geyer J, Orazi A. Myeloproliferative neoplasms (BCR‐ABL1 negative) and myelodysplastic/myeloproliferative neoplasms: current diagnostic principles and upcoming updates. Int J Lab Hematol 2016; 38: 12-9. 5. Kaplan JB, Stein BL, McMahon B, Giles FJ, Platanias LC. Evolving therapeutic strategies for the classic Philadelphia-negative myeloproliferative neoplasms. EBio Med 2016; 3: 17-25. 6. Geyer HL, Mesa RA. Therapy for myeloproliferative neoplasms: when, which agent, and how? Blood 2014; 124: 3529-37. 7. Tefferi A. Mutations galore in myeloproliferative neoplasms: would the real Spartacus please stand up? : Nature Publishing Group; 2011. 8. Klampfl T, Gisslinger H, Harutyunyan AS, Nivarthi H, Rumi E, Milosevic JD, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. New Eng J Med 2013; 369: 2379-90. 9. Nangalia J, Massie CE, Baxter EJ, Nice FL, Gundem G, Wedge DC, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. New Eng J Med 2013; 369: 2391-405. 10. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: e270. 11. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472-6. 12. Emanuel RM, Dueck AC, Geyer HL, Kiladjian J-J, Slot S, Zweegman S, et al. Myeloproliferative neoplasm (MPN) symptom assessment form total symptom score: prospective international assessment of an abbreviated symptom burden scoring system among patients with MPNs. J Clin Oncol 2012; 30: 4098. 13. Geyer HL, Scherber RM, Dueck AC, Kiladjian J-J, Xiao Z, Slot S, et al. Distinct clustering of symptomatic burden among myeloproliferative neoplasm patients: retrospective assessment in 1470 patients. Blood 2014; 123: 3803-10. 14. Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 2011; 29: 3179-84. 15. Tefferi A, Rumi E, Finazzi G, Gisslinger H, Vannucchi A, Rodeghiero F, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013; 27: 1874. 16. Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, et al. DIPSS-plus: DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 2011; 29: 392-7. 17. Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 2010; 115: 1703-8. 18. Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009; 113: 2895-901. 19. Kaifie A, Kirschner M, Wolf D, Maintz C, Hänel M, Gattermann N, et al. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol 2016; 9: 18. 20. Mesa R, Miller CB, Thyne M, Mangan J, Goldberger S, Fazal S, et al. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and productivity: the MPN Landmark survey. BMC Cancer 2016; 16: 167. 21. Scherber R, Dueck AC, Johansson P, Barbui T, Barosi G, Vannucchi AM, et al. The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): international prospective validation and reliability trial in 402 patients. Blood 2011; 118: 401-8. 22. Johansson P, Mesa R, Scherber R, Abelsson J, Samuelsson J, Birgegård G, et al. Association between quality of life and clinical parameters in patients with myeloproliferative neoplasms. Leuk Lymphoma 2012; 53: 441-4. 23. Abelsson J, Andréasson B, Samuelsson J, Hultcrantz M, Ejerblad E, Johansson B, et al. Patients with polycythemia vera have worst impairment of quality of life among patients with newly diagnosed myeloproliferative neoplasms. Leuk Lymphoma 2013; 54: 2226-30. 25. Mesa RA, Niblack J, Wadleigh M, Verstovsek S, Camoriano J, Barnes S, ve ark. The burden of fatigue and quality of life in myeloproliferative disorders (MPDs). Cancer 2007; 109: 68-76. 26. da Costa Cacemiro M, Cominal JG, Tognon R, de Souza Nunes N, Simões BP, de Figueiredo-Pontes LL, et al. Philadelphia-negative myeloproliferative neoplasms as disorders marked by cytokine modulation. Hematol Transfus Cell Ther 2018. 27. Jinquan T, Quan S, Jacobi HH, Jing C, Millner A, Jensen B, et al. CXC chemokine receptor 3 expression on CD34+ hematopoietic progenitors from human cord blood induced by granulocyte-macrophage colony-stimulating factor: chemotaxis and adhesion induced by its ligands, interferon γ-inducible protein 10 and monokine induced by interferon γ. Blood 2000; 96: 1230-8. 28. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 2001; 25: 402-8. 29. Callahan MK, Williams KA, Kivisäkk P, Pearce D, Stins MF, Ransohoff RM. CXCR3 marks CD4+ memory T lymphocytes that are competent to migrate across a human brain microvascular endothelial cell layer. J Neuroimmunol 2004; 153: 150-7. 30. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 1994; 76: 301-14. 31. Baggiolini M. Chemokines and leukocyte traffic. Nature 1998; 392: 565. 32. Glaser J, Gonzalez R, Perreau VM, Cotman CW, Keirstead HS. Neutralization of the chemokine CXCL10 enhances tissue sparing and angiogenesis following spinal cord injury. J Neurosci Res 2004; 77: 701-8. 33. Kelsen SG, Aksoy MO, Yang Y, Shahabuddin S, Litvin J, Safadi F, et al. The chemokine receptor CXCR3 and its splice variant are expressed in human airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 2004; 287: L584-91. 34. Chakraborty K, Bose A, Pal S, Chattopadhyay U, Baral R. Interferon-α2b Restores the Impaired Chemotactic Activity of Peripheral Blood Mononuclear Cells from Head and Neck Squamous Cell Carcinoma Patients by Modulating CXC Receptor Ligand Interaction. J Interferon Cytokine Res 2007; 28: 487-500. 35. Chakraborty K, Bose A, Pal S, Sarkar K, Goswami S, Ghosh D, et al. Neem leaf glycoprotein restores the impaired chemotactic activity of peripheral blood mononuclear cells from head and neck squamous cell carcinoma patients by maintaining CXCR3/CXCL10 balance. Int Immunopharmacol 2008; 8: 330-40. 36. Furuya M, Yoneyama T, Miyagi E, Tanaka R, Nagahama K, Miyagi Y, et al. Differential expression patterns of CXCR3 variants and corresponding CXC chemokines in clear cell ovarian cancers and endometriosis. Gynecol Oncol 2011; 122: 648-55. 37. Wu Q, Dhir R, Wells A. Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion. Mol Cancer 2012; 11: 3. 38. Datta D, Contreras AG, Grimm M, Waaga-Gasser AM, Briscoe DM, Pal S. Calcineurin inhibitors modulate CXCR3 splice variant expression and mediate renal cancer progression. J American Soc Nephrol 2008; 19: 2437-46. 39. Romagnani P, Beltrame C, Annunziato F, Lasagni L, Luconi M, Galli G, et al. Role for interactions between IP-10/Mig and CXCR3 in proliferative glomerulonephritis. J American Soc Nephrol 1999; 10: 2518-26. 40. Romagnani P, Lazzeri E, Lasagni L, Mavilia C, Beltrame C, Francalanci M, et al. IP-10 and Mig production by glomerular cells in human proliferative glomerulonephritis and regulation by nitric oxide. J American Soc Nephrol 2002; 13: 53-64. 41. Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res 2006; 4: 221-33. 42. Perwez Hussain S, Harris CC. Inflammation and cancer: an ancient link with novel potentials. Int J Cancer 2007; 121: 2373-80. 43. Maeda H, Akaike T. Nitric oxide and oxygen radicals in infection, inflammation, and cancer. Biochemistry 1998; 63: 854-65. 44. Ma B, Khazali A, Wells A. CXCR3 in carcinoma progression. Histol Histopathol 2015; 30: 781. 45. Lleo A, Zhang W, Zhao M, Tan Y, Bernuzzi F, Zhu B, et al. DNA methylation profiling of the X chromosome reveals an aberrant demethylation on CXCR3 promoter in primary biliary cirrhosis. Clin Epigenetics 2015; 7: 61. 46. Kumar DSS, Wells A. CXCR3 epigenome switches splice variants in prostate cancer. AACR; 2013. 47. Urra S, Fischer MC, Martínez JR, Véliz L, Orellana P, Solar A, et al. Differential expression profile of CXCR3 splicing variants is associated with thyroid neoplasia. Potential role in papillary thyroid carcinoma oncogenesis? Oncotarget 2018; 9: 2445. 48. Witte E, Kokolakis G, Witte K, Warszawska K, Friedrich M, Christou D, et al. Interleukin-29 induces epithelial production of CXCR3A ligands and T-cell infiltration. J Mol Med 2016; 94: 391-400. 49. Walters JH, Mc GI. The mechanism of malarial hepatomegaly and its relationship to hepatic fibrosis. Trans R Soc Trop Med Hyg 1960; 54: 135-45. 50. Van Raemdonck K, Van den Steen PE, Liekens S, Van Damme J, Struyf S. CXCR3 ligands in disease and therapy. Cytokine Growth Factor Rev 2015; 26: 311-27. 51. Wasmuth H, Weiskirchen R. Pathogenesis of liver fibrosis: modulation of stellate cells by chemokines. Zeitschrift fur Gastroenterologie 2010; 48: 38-45. 52. Li J, Liu B, Shi Y, Xie K-L, Yin H-F, Yan L-n, et al. CXCL4 Contributes to the Pathogenesis of Chronic Liver Allograft Dysfunction. J Immunol Res 2016; 2016: 9276986. 53. Baldi P, Long AD. A Bayesian framework for the analysis of microarray expression data: regularized t-test and statistical inferences of gene changes. Bioinformatics 2001; 17: 509-19. 54. Szallasi Z. Genetic network analysis in light of massively parallel biological data acquisition. Pac Symp Biocomput 1999; 5-16. 55. Colvin RA, Campanella GS, Sun J, Luster AD. Intracellular domains of CXCR3 that mediate CXCL9, CXCL10, and CXCL11 function. J Biol Chem 2004; 279: 30219-27. 56. Meiser A, Mueller A, Wise EL, McDonagh EM, Petit SJ, Saran N, ve ark. The chemokine receptor CXCR3 is degraded following internalization and is replenished at the cell surface by de novo synthesis of receptor. J Immunol 2008; 180: 6713-24. 57. Wu Q, Dhir R, Wells A. Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion. Mol Cancer 2012; 11: 3.
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Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Cemil Altunay This is me

Akif Selim Yavuz This is me

Selçuk Sözer Tokdemir

Publication Date December 2, 2018
Submission Date November 27, 2018
Published in Issue Year 2018 Volume: 8 Issue: 3

Cite

Vancouver Altunay C, Yavuz AS, Sözer Tokdemir S. Effect of CXCL9-CXCR3 Cytokine Signaling Pathway in Polycytemia Vera. Experimed. 2018;8(3):84-92.