Overexpression of Semaphorin-3A and Semaphorin-4D in the Peripheral Blood from Newly Diagnosed Patients with Chronic Lymphocytic Leukemia

  • Somayeh Parsa Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  • Sedigheh Sharifzadeh Diagnostic Laboratory Science and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  • Ahmad Monabati Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
  • Noorossadat Seyyedi Diagnostic Laboratory Science and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  • Reza Ranjbaran Diagnostic Laboratory Science and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  • Mohammad Reza Baghbani Diagnostic Laboratory Science and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
  • Maryam Nemati Department of Laboratory Sciences, School of Para-Medicine, Kerman University of Medical Sciences, kerman, Iran
  • Abdollah Jafarzadeh 1) Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran 2) Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
Keywords: Chronic lymphocytic leukemia; Semaphorins; SEMA3A; SEMA4A; SEMA4D

Abstract

Background: Semaphorins play prominent roles in physiological and pathological processes such as vascular development, tumor growth and immune responses. Semaphorins have different roles in various kinds of cancers, but there is no study concerning their expression in the chronic lymphocytic leukemia (CLL). This study aimed to assess the SEMA3A, SEMA4A and SEMA4D expression in patients with CLL.  Materials and Methods: Peripheral blood specimens were collected from 30 newly-diagnosed untreated patients with CLL and 30 healthy subjects as a control group. The SEMA3A, SEMA4A and SEMA4D expression was determined by real-time PCR method.  Results: The fold change expression of SEMA3A and SEMA4D was 7.58 ± 2.66 and 3.20 ± 0.99 in patients with CLL, and was 1.01 ± 0.31 and 1.00 ± 0.27 in healthy subjects, respectively. The CLL patients expressed higher amounts of SEMA3A and SEMA4D in comparison with healthy subjects (P<0.02 and P<0.03, respectively). The fold change expression of SEMA3A in patients with stage II (11.12 ± 5.35) was also higher than patients with stage I (4.49 ± 1.61, P<0.05). No significant difference was also observed in the expression of SEMA4A and SEMA4D between patients with stage I and stage II CLL. In both CLL and control groups, the fold change expression of SEMA3A was higher in men than in women (P<0.03 and P<0.02, respectively). Conclusion: The results of the study indicated elevated expression of the SEMA3A and SEMA4D in patients with CLL. The SEMA3A expression was influenced by tumor stage and gender of participants.   

References

References

Hallek M. Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment. Am J Hematol 2017; 92: 946-965.

Scarfo L, Ferreri AJ, Ghia P. Chronic lymphocytic leukaemia. Crit Rev Oncol Hematol 2016; 104: 169-182.

Slager SL, Caporaso NE, de Sanjose S, Goldin LR. Genetic susceptibility to chronic lymphocytic leukemia. Semin Hematol 2013; 50: 296-302.

Yu EM, Kittai A, Tabbara IA. Chronic Lymphocytic Leukemia: Current Concepts. Anticancer Res 2015; 35: 5149-5165.

Goodman C, Kolodkin A, Luo Y, Püschel A, Raper J. Unified nomenclature for the semaphorins/collapsins. Cell 1999; 97: 551-552.

Neufeld G, Mumblat Y, Smolkin T, Toledano S, Nir-Zvi I, Ziv K, Kessler O. The role of the semaphorins in cancer. Cell Adh Migr 2016; 10: 652-674.

Neufeld G, Sabag AD, Rabinovicz N, Kessler O. Semaphorins in angiogenesis and tumor progression. Cold Spring Harb Perspect Med 2012; 2: a006718.

Ali I, Chouhan VS, Dangi SS, Gupta M, Tandiya U, Hyder I, Yadav VP, Panda RP, Babitha V, Nagar V. Expression and localization of locally produced growth factors regulating lymphangiogenesis during different stages of the estrous cycle in corpus luteum of buffalo (Bubalus bubalis). Theriogenology 2014; 81: 428-436.

Yazdani U, Terman JR. The semaphorins. Genome Biol 2006; 7:211.

Giacobini P, Prevot V. Semaphorins in the development, homeostasis and disease of hormone systems. Semin Cell Dev Biol 2013; 24: 190-198.

Eissler N, Rolny C. The role of immune semaphorins in cancer progression. Exp Cell Res 2013; 319: 1635-1643.

Ito D, Kumanogoh A. The role of Sema4A in angiogenesis, immune responses, carcinogenesis, and retinal systems. Cell Adh Migr 2016; 10: 692-699.

Neufeld G, Kessler O. The semaphorins: versatile regulators of tumour progression and tumour angiogenesis. Nat Rev Cancer 2008; 8: 632-645.

Jafarzadeh A, Fooladseresht H, Minaee K, Bazrafshani MR, Khosravimashizi A, Nemati M, Mohammadizadeh M, Mohammadi MM, Ghaderi A. Higher circulating levels of chemokine CCL22 in patients with breast cancer: evaluation of the influences of tumor stage and chemokine gene polymorphism. Tumour Biol 2015; 36: 1163-1171.

Jafarzadeh A, Minaee K, Farsinejad AR, Nemati M, Khosravimashizi A, Daneshvar H, Mohammadi MM, Sheikhi A, Ghaderi A. Evaluation of the circulating levels of IL-12 and IL-33 in patients with breast cancer: influences of the tumor stages and cytokine gene polymorphisms. Iran J Basic Med Sci 2015; 18: 1189-1198.

Jafarzadeh A, Fooladseresht H, Nemati M, Assadollahi Z, Sheikhi A, Ghaderi A. Higher circulating levels of chemokine CXCL10 in patients with breast cancer: Evaluation of the influences of tumor stage and chemokine gene polymorphism. Cancer Biomark 2016; 16: 545-554.

Sheikhi A, Jafarzadeh A, Kokhaei P, Hojjat-Farsangi M. Whole Tumor Cell Vaccine Adjuvants: Comparing IL-12 to IL-2 and IL-15. Iran J Immunol 2016; 13: 148-166.

Sheikhi A, Jafarzadeh A. A new therapeutic potential for cancers: One CAR with 2 different engines! Hum Vaccin Immunother 2017; 13: 1786-1788.

Ghia P, Ferreri AM, Caligaris-Cappio F. Chronic lymphocytic leukemia. Crit Rev Oncol Hematol 2007; 64: 234-246.

Binet JL, Caligaris-Cappio F, Catovsky D, Cheson B, Davis T, Dighiero G, Dohner H, Hallek M, Hillmen P, Keating M, Montserrat E, Kipps TJ, Rai K. Perspectives on the use of new diagnostic tools in the treatment of chronic lymphocytic leukemia. Blood 2006; 107: 859-861.

Casazza A, Fu X, Johansson I, Capparuccia L, Andersson F, Giustacchini A, Squadrito ML, Venneri MA, Mazzone M, Larsson E, Carmeliet P, De Palma M, Naldini L, Tamagnone L, Rolny C. Systemic and targeted delivery of semaphorin 3A inhibits tumor angiogenesis and progression in mouse tumor models. Arterioscler Thromb Vasc Biol 2011; 31: 741-749.

Zhou H, Wu A, Fu W, Lv Z, Zhang Z. Significance of semaphorin-3A and MMP-14 protein expression in non-small cell lung cancer. Oncol Lett 2014; 7: 1395-1400.

Chakraborty G, Kumar S, Mishra R, Patil TV, Kundu GC. Semaphorin 3A suppresses tumor growth and metastasis in mice melanoma model. PLoS One 2012; 7: e33633.

Vadasz Z, Rubinstein J, Bejar J, Sheffer H, Halachmi S. Overexpression of semaphorin 3A in patients with urothelial cancer. Urol Oncol 2017; pii: S1078-1439: 30620-8.

Bagci T, Wu JK, Pfannl R, Ilag LL, Jay DG. Autocrine semaphorin 3A signaling promotes glioblastoma dispersal. Oncogene 2009; 28: 3537-2550.

Hu ZQ, Zhou SL, Zhou ZJ, Luo CB, Chen EB, Zhan H, Wang PC, Dai Z, Zhou J, Fan J, Huang XW. Overexpression of semaphorin 3A promotes tumor progression and predicts poor prognosis in hepatocellular carcinoma after curative resection. Oncotarget 2016; 7: 51733-51746.

Li X, Chen Q, Yin D, Shi S, Yu L, Zhou S, Chen E, Zhou Z, Shi Y, Fan J, Zhou J, Dai Z. Novel role of semaphorin 3A in the growth and progression of hepatocellular carcinoma. Oncol Rep 2017; 37: 3313-3320.

Yamada D, Takahashi K, Kawahara K, Maeda T. Autocrine Semaphorin3A signaling is essential for the maintenance of stem-like cells in lung cancer. Biochem Biophys Res Commun 2016; 480: 375-379.

Ch'ng E, Tomita Y, Zhang B, He J, Hoshida Y, Qiu Y, Morii E, Nakamichi I, Hamada Ki, Ueda T. Prognostic significance of CD100 expression in soft tissue sarcoma. Cancer 2007; 110: 164-172.

Kato S, Kubota K, Shimamura T, Shinohara Y, Kobayashi N, Watanabe S, Yoneda M, Inamori M, Nakamura F, Ishiguro H. Semaphorin 4D, a lymphocyte semaphorin, enhances tumor cell motility through binding its receptor, plexinB1, in pancreatic cancer. Cancer Sci 2011; 102: 2029-2037.

Sierra JR, Corso S, Caione L, Cepero V, Conrotto P, Cignetti A, Piacibello W, Kumanogoh A, Kikutani H, Comoglio PM. Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages. The Journal of experimental medicine 2008; 205: 1673-1685.

Bismuth G, Boumsell L. Controlling the immune system through semaphorins. Sci STKE 2002.; 2002: re4.

Valente G, Nicotra G, Arrondini M, Castino R, Capparuccia L, Prat M, Kerim S, Tamagnone L, Isidoro C. Co-expression of plexin-B1 and Met in human breast and ovary tumours enhances the risk of progression. Cell Oncol 2009; 31: 423-436.

Nkyimbeng-Takwi E, Chapoval SP. Biology and function of neuroimmune semaphorins 4A and 4D. Immunol Res 2011; 50: 10-21.

Ito D, Nojima S, Nishide M, Okuno T, Takamatsu H, Kang S, Kimura T, Yoshida Y, Morimoto K, Maeda Y, Hosokawa T, Toyofuku T, Ohshima J, Kamimura D, Yamamoto M, Murakami M, Morii E, Rakugi H, Isaka Y, Kumanogoh A. mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells. J Immunol 2015; 195: 934-943.

Delgoffe GM, Woo SR, Turnis ME, Gravano DM, Guy C, Overacre AE, Bettini ML, Vogel P, Finkelstein D, Bonnevier J, Workman CJ, Vignali DA. Stability and function of regulatory T cells is maintained by a neuropilin-1-semaphorin-4a axis. Nature 2013; 501: 252-6.

Karayan-Tapon L, Wager M, Guilhot J, Levillain P, Marquant C, Clarhaut J, Potiron V, Roche J. Semaphorin, neuropilin and VEGF expression in glial tumours: SEMA3G, a prognostic marker? Br J Cancer 2008; 99: 1153-60.

Published
2019-01-02
How to Cite
1.
Parsa S, Sharifzadeh S, Monabati A, Seyyedi N, Ranjbaran R, Baghbani MR, Nemati M, Jafarzadeh A. Overexpression of Semaphorin-3A and Semaphorin-4D in the Peripheral Blood from Newly Diagnosed Patients with Chronic Lymphocytic Leukemia. ijhoscr. 13(01):25-4.
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