Calreticulin Regulates VEGF-A in Neuroblastoma Cells

详细信息    查看全文

• 作者：Wen-Chin Weng ; Kuan-Hung Lin ; Pei-Yi Wu ; Yi-Chien Lu…
• 关键词：Calreticulin ; VEGF ; Neuroblastoma ; Neuronal differentiation
• 刊名：Molecular Neurobiology
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：52
• 期：1
• 页码：758-770
• 全文大小：1,250 KB
• 参考文献：1.Brodeur GM (2003) Neuroblastoma: biological insights into a clinical enigma. Nat Rev Cancer 3(3):203-16. doi:10.-038/?nrc1014 PubMed View Article
  2.Chang HH, Hsu WM (2010) Neuroblastoma—a model disease for childhood cancer. J Formos Med Assoc 109(8):555-57PubMed View Article
  3.Maris JM, Hogarty MD, Bagatell R, Cohn SL (2007) Neuroblastoma. Lancet 369(9579):2106-120. doi:10.-016/?s0140-6736(07)60983-0 PubMed View Article
  4.Israel MA (1993) Disordered differentiation as a target for novel approaches to the treatment of neuroblastoma. Cancer 71(10 Suppl):3310-313PubMed View Article
  5.Ijiri R, Tanaka Y, Kato K, Misugi K, Nishihira H, Toyoda Y, Kigasawa H, Nishi T, Takeuchi M, Aida N, Momoi T (2000) Clinicopathologic study of mass-screened neuroblastoma with special emphasis on untreated observed cases: a possible histologic clue to tumor regression. Am J Surg Pathol 24(6):807-15PubMed View Article
  6.Nishihira H, Toyoda Y, Tanaka Y, Ijiri R, Aida N, Takeuchi M, Ohnuma K, Kigasawa H, Kato K, Nishi T (2000) Natural course of neuroblastoma detected by mass screening: s 5-year prospective study at a single institution. J Clin Oncol 18(16):3012-017PubMed
  7.Nakagawara A, Arima-Nakagawara M, Scavarda NJ, Azar CG, Cantor AB, Brodeur GM (1993) Association between high levels of expression of the TRK gene and favorable outcome in human neuroblastoma. N Engl J Med 328(12):847-54. doi:10.-056/?nejm199303253281-05 PubMed View Article
  8.Hoehner JC, Gestblom C, Olsen L, Pahlman S (1997) Spatial association of apoptosis-related gene expression and cellular death in clinical neuroblastoma. Br J Cancer 75(8):1185-194PubMed Central PubMed View Article
  9.Michalak M, Corbett EF, Mesaeli N, Nakamura K, Opas M (1999) Calreticulin: one protein, one gene, many functions. Biochem J 344(Pt 2):281-92PubMed Central PubMed View Article
  10.Lu YC, Chen CN, Wang B, Hsu WM, Chen ST, Chang KJ, Chang CC, Lee H (2011) Changes in tumor growth and metastatic capacities of J82 human bladder cancer cells suppressed by down-regulation of calreticulin expression. Am J Pathol 179(3):1425-433. doi:10.-016/?j.?ajpath.-011.-5.-15 PubMed Central PubMed View Article
  11.Xiao G, Chung TF, Pyun HY, Fine RE, Johnson RJ (1999) KDEL proteins are found on the surface of NG108-15 cells. Brain Res Mol Brain Res 72(2):121-28PubMed View Article
  12.Xiao G, Chung TF, Fine RE, Johnson RJ (1999) Calreticulin is transported to the surface of NG108-15 cells where it forms surface patches and is partially degraded in an acidic compartment. J Neurosci Res 58(5):652-62PubMed View Article
  13.Johnson RJ, Liu N, Shanmugaratnam J, Fine RE (1998) Increased calreticulin stability in differentiated NG-108-15 cells correlates with resistance to apoptosis induced by antisense treatment. Brain Res Mol Brain Res 53(1-):104-11PubMed View Article
  14.Hsu WM, Hsieh FJ, Jeng YM, Kuo ML, Chen CN, Lai DM, Hsieh LJ, Wang BT, Tsao PN, Lee H, Lin MT, Lai HS, Chen WJ (2005) Calreticulin expression in neuroblastoma—a novel independent prognostic factor. Ann Oncol 16(2):314-21. doi:10.-093/?annonc/?mdi062 PubMed View Article
  15.Ferrara N, Gerber HP, LeCouter J (2003) The biology of VEGF and its receptors. Nat Med 9(6):669-76. doi:10.-038/?nm0603-669 PubMed View Article
  16.George ML, Tutton MG, Janssen F, Arnaoutz A, Abulafi AM, Eccles SA, Swift RI (2001) VEGF-A, VEGF-C, and VEGF-D in colorectal cancer progression. Neoplasia 3(5):420-27. doi:10.-038/?sj.?neo.-900186 PubMed Central PubMed View Article
  17.B?ckman U, Svensson ?, Christofferson R (2002) Importance of vascular endothelial growth factor A in the progression of experimental neuroblastoma. Angiogenesis 5(4):267-74. doi:10.-023/?A:-024564817563 PubMed View Article
  18.Fakhari M, Pullirsch D, Paya K, Abraham D, Hofbauer R, Aharinejad S (2002) Upregulation of vascular endothelial growth factor receptors is associated with advanced neuroblastoma. J Pediatr Surg 37(4):582-87. doi:10.-053/?jpsu.-002.-1614 PubMed View Article
  19.Becker J, Pavlakovic H, Ludewig F, Wilting F, Weich HA, Albuquerque R, Ambati J, Wilting J (2010) Neuroblastoma progression correlates with downregulation of the lymphangiogenesis inhibitor sVEGFR-2. Clin Cancer Res 16(5):1431-441. doi:10.-158/-078-0432.?CCR-09-1936 PubMed Central PubMed View Article
  20.Chen CN, Chang CC, Su TE, Hsu WM, Jeng YM, Ho MC, Hsieh FJ, Lee PH, Kuo ML, Lee H, Chang KJ (2009) Identification of calreticulin as a prognosis marker and angiogenic regulator in human gastric cancer. Ann Surg Oncol 16(2):524-33. doi:10.-245/?s10434-008-0243-1 PubMed View Article
  21.Porebska I, Wyrodek E, Kosacka M, Adamiak J, Jankowska R, Harlozinska-Szmyrka A (2006) Apoptotic markers p53, Bcl-2 and Bax in primary lung cancer. In Vivo 20(5):599-04PubMed
  22.Puppo M, Battaglia F, Ottaviano C, Delfino S, Ribatti D, Varesio L, Bosco MC (2008) Topotecan inhibits vascular endothelial growth factor production
• 作者单位：Wen-Chin Weng (1) (2)
  Kuan-Hung Lin (2)
  Pei-Yi Wu (2)
  Yi-Chien Lu (2)
  Yi-Cheng Weng (2)
  Bo-Jeng Wang (3)
  Yung-Feng Liao (3)
  Wen-Ming Hsu (4)
  Wang-Tso Lee (1)
  Hsinyu Lee (2) (5) (6) (7) (8)
  
  1. Department of Pediatrics, College of Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan
  2. Department of Life Science, National Taiwan University, Taipei, Taiwan
  3. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan
  4. Department of Surgery, College of Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan
  5. Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan
  6. Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan
  7. Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
  8. Center for Biotechnology, National Taiwan University, Taipei, Taiwan
  
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182

文摘

Calreticulin (CRT) has been previously correlated with the differentiation of neuroblastoma (NB), implying a favorable prognostic factor. Vascular endothelial growth factor (VEGF) has been reported to participate in the behavior of NB. This study investigated the association of CRT and VEGF-A in NB cells. The expressions of VEGF-A and HIF-1α, with overexpression or knockdown of CRT, were measured in three NB cells (SH-SY5Y, SK-N-DZ, and stNB-V1). An inducible CRT NB cell line and knockdown CRT stable cell lines were also established. The impacts of CRT overexpression on NB cell apoptosis, proliferation, and differentiation were also evaluated. We further examined the role of VEGF-A in the NB cell differentiation via VEGF receptor blockade. Constitutive overexpression of CRT led to NB cell differentiation without proliferation. Thus, an inducible CRT stNB-V1 cell line was generated by a tetracycline-regulated gene system. CRT overexpression increased VEGF-A and HIF-1α messenger RNA (mRNA) expressions in SH-SY5Y, SK-N-DZ, and stNB-V1 cells. CRT overexpression also enhanced VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. Knockdown of CRT decreased VEGF-A and HIF-1α mRNA expressions and lowered VEGF-A protein expression and secretion level in conditioned media in different NB cell lines. We further demonstrated that NB cell apoptosis was not affected by CRT overexpression in stNB-V1 cells. Nevertheless, overexpression of CRT suppressed cell proliferation and enhanced cell differentiation in stNB-V1 cells, whereas blockage of VEGFR-1 markedly suppressed the expression of neuron-specific markers including GAP43, NSE2, and NFH, as well as TrkA, a molecular marker indicative of NB cell differentiation. Our findings suggest that VEGF-A is involved in CRT-related neuronal differentiation in NB. Our work may provide important information for developing a new therapeutic strategy to improve the outcome of NB patients.