B7-H3 overexpression in pancreatic cancer promotes tumor progression

Zhao,Xin; Li,De-Chun; Zhu,Xin-Guo; Gan,Wen-Juan; Li,Zhi; Xiong,Feng; Zhang,Zi-Xiang; Zhang,Guang-Bo; Zhang,Xue-Guang; Zhao,Hua

doi:10.3892/ijmm.2012.1212

B7-H3 overexpression in pancreatic cancer promotes tumor progression

Authors:
- Xin Zhao
- De-Chun Li
- Xin-Guo Zhu
- Wen-Juan Gan
- Zhi Li
- Feng Xiong
- Zi-Xiang Zhang
- Guang-Bo Zhang
- Xue-Guang Zhang
- Hua Zhao
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China, Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China, Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China, Department of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China
Published online on: December 13, 2012 https://doi.org/10.3892/ijmm.2012.1212
Pages: 283-291
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

B7-H3, a member of the B7-family molecules, plays an important role in adaptive immune responses. In addition, B7-H3 is also expressed in several types of human cancers and is correlated with the poor outcome of cancer patients. However, its exact role in cancer is not known. In the present study, we compared B7-H3 expression in normal pancreas and pancreatic cancer tissue specimens, and determined the effects of low B7-H3 expression on the human pancreatic cancer cell line Patu8988 using lentivirus-mediated RNA interference. B7-H3 expression in pancreatic specimens was determined by enzyme-linked immunosorbent assay (ELISA). A Patu8988 cell line with low B7-H3 expression was established by lentivirus-mediated RNA interference to investigate the effect of B7-H3 on cell proliferation, migration and invasion in vitro. By establishing subcutaneous transplantation tumor and orthotopic transplantation pancreatic cancer mouse models, the effect of B7-H3 on cell proliferation, migration and invasion was studied in vivo. B7-H3 in tissue samples was significantly higher in the pancreatic cancer group than in the normal pancreas group (mean ± SD, 193.6±9.352 vs. 87.74±7.433 ng/g; P<0.0001). B7-H3 knockdown by RNA interference decreased cell migration and Transwell invasion up to 50% in vitro. No apparent impact was observed on cell proliferation in vitro. In the subcutaneous transplantation tumor mouse model, the tumor growth rate was reduced by the knockdown of B7-H3. In the orthotopic transplantation pancreatic cancer mouse model, the effect of inhibiting metastasis by knocking down B7-H3 was assessed in terms of the average postmortem abdominal visceral metastatic tumor weight. This demonstrated that inhibition of B7-H3 expression reduced pancreatic cancer metastasis in vivo. In conclusion, B7-H3 is aberrantly expressed in pancreatic cancer. In addition to modulating tumor immunity, B7-H3 may have a novel role in regulating pancreatic tumor progression.

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1	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar
2	Neoptolemos JP, Cunningham D, Friess H, et al: Adjuvant therapy in pancreatic cancer: historical and current perspectives. Ann Oncol. 14:675–692. 2003. View Article : Google Scholar : PubMed/NCBI
3	Hidalgo M: Pancreatic cancer. N Engl J Med. 362:1605–1617. 2010. View Article : Google Scholar
4	Ghaneh P, Costello E, Neoptolemos JP, et al: Biology and management of pancreatic cancer. Postgrad Med J. 84:478–497. 2008. View Article : Google Scholar
5	Pan X, Sheng W, Zhu Q, et al: Inhibition of pancreatic carcinoma growth by adenovirus-mediated human interleukin-24 expression in animal model. Cancer Biother Radiopharm. 23:425–434. 2008. View Article : Google Scholar : PubMed/NCBI
6	Zhou J, Zhang ZX, Zhao H, et al: Anti-angiogenesis by lentivirus-mediated small interfering RNA silencing of angiopoietin-2 gene in pancreatic carcinoma. Technol Cancer Res Treat. 10:361–369. 2011.PubMed/NCBI
7	Zhao X, Li DC, Zhao H, et al: A study of the suppressive effect on human pancreatic adenocarcinoma cell proliferation and angiogenesis by stable plasmid-based siRNA silencing of c-Src gene expression. Oncol Rep. 27:628–636. 2012.PubMed/NCBI
8	Chapoval AI, Ni J, Lau JS, et al: B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol. 2:269–274. 2001. View Article : Google Scholar : PubMed/NCBI
9	Suh WK, Wang SX, Jheon AH, et al: The immune regulatory protein B7-H3 promotes osteoblast differentiation and bone mineralization. Proc Natl Acad Sci USA. 101:12969–12973. 2004. View Article : Google Scholar : PubMed/NCBI
10	Steinberger P, Majdic O, Derdak SV, et al: Molecular characterization of human 4Ig-B7-H3, a member of the B7 family with four Ig-like domains. J Immunol. 172:2352–2359. 2004. View Article : Google Scholar : PubMed/NCBI
11	Zhang GB, Zhou H, Chen YJ, et al: Characterization and application of two novel monoclonal antibodies against 2IgB7-H3: expression analysis of 2IgB7-H3 on dendritic cells and tumor cells. Tissue Antigens. 66:83–92. 2005. View Article : Google Scholar : PubMed/NCBI
12	Yamato I, Sho M, Nomi T, et al: Clinical importance of B7-H3 expression in human pancreatic cancer. Br J Cancer. 101:1709–1716. 2009. View Article : Google Scholar : PubMed/NCBI
13	Luo L, Chapoval AI, Flies DB, et al: B7-H3 enhances tumor immunity in vivo by costimulating rapid clonal expansion of antigen-specific CD8⁺ cytolytic T cells. J Immunol. 173:5445–5450. 2004. View Article : Google Scholar : PubMed/NCBI
14	Lupu CM, Eisenbach C, Kuefner MA, et al: An orthotopic colon cancer model for studying the B7-H3 antitumor effect in vivo. J Gastrointest Surg. 10:635–645. 2006. View Article : Google Scholar : PubMed/NCBI
15	Castriconi R, Dondero A, Augugliaro R, et al: Identification of 4Ig-B7-H3 as a neuroblastoma associated molecule that exerts a protective role from an NK cell-mediated lysis. Proc Natl Acad Sci USA. 101:12640–12645. 2004. View Article : Google Scholar : PubMed/NCBI
16	Suh WK, Gajewska BU, Okada H, et al: The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat Immunol. 4:899–906. 2003. View Article : Google Scholar : PubMed/NCBI
17	Prasad DV, Nguyen T, Li Z, et al: Murine B7-H3 is a negative regulator of T cells. J Immunol. 173:2500–2506. 2004. View Article : Google Scholar : PubMed/NCBI
18	Fukushima A, Sumi T, Fukuda K, et al: B7-H3 regulates the development of experimental allergic conjunctivitis in mice. Immunol Lett. 113:52–57. 2007. View Article : Google Scholar : PubMed/NCBI
19	Ghadially R: The role of stem and circulating cells in cancer metastasis. J Surg Oncol. 103:555–557. 2011. View Article : Google Scholar : PubMed/NCBI
20	Chaffer CL and Weinberg RA: A perspective on cancer cell metastasis. Science. 331:1559–1564. 2011. View Article : Google Scholar : PubMed/NCBI
21	Chen YW, Tekle C and Fodstad O: The immunoregulatory protein human B7-H3 is a tumor-associated antigen that regulates tumor cell migration and invasion. Curr Cancer Drug Targets. 8:404–413. 2008. View Article : Google Scholar : PubMed/NCBI
22	Zhang G, Hou J, Shi J, et al: Soluble CD276 (B7-H3) is released from monocytes, dendritic cells and activated T cells and is detectable in normal human serum. Immunology. 123:538–546. 2008. View Article : Google Scholar : PubMed/NCBI
23	Tsai CY, Lee TS, Kou YR, et al: Glucosamine inhibits IL-1 beta-mediated IL-8 production in prostate cancer cells by MAPK attenuation. J Cell Biochem. 108:489–498. 2009. View Article : Google Scholar : PubMed/NCBI
24	Fernandez-Martinez AB, Bajo AM, Sanchez-Chapado M, et al: Vasoactive intestinal peptide behaves as a pro-metastatic factor in human prostate cancer cells. Prostate. 69:774–786. 2009. View Article : Google Scholar : PubMed/NCBI
25	Yaqinuddin A, Qureshi SA, Qazi R, et al: DNMT1 silencing affects locus specific DNA methylation and increases prostate cancer derived PC3 cell invasiveness. J Urol. 182:756–761. 2009. View Article : Google Scholar : PubMed/NCBI
26	ElBayoumi TA and Torchilin VP: Tumor-targeted nano-medicines: enhanced antitumor efficacy in vivo of doxorubicin-loaded, long-circulating liposomes modified with cancer-specific monoclonal antibody. Clin Cancer Res. 15:1973–1980. 2009. View Article : Google Scholar
27	Wu CP, Jiang JT, Tan M, et al: Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis. World J Gastroenterol. 12:457–459. 2006.PubMed/NCBI
28	Zhang G, Xu Y, Lu X, et al: Diagnosis value of serum B7-H3 expression in non-small cell lung cancer. Lung Cancer. 66:245–249. 2009. View Article : Google Scholar : PubMed/NCBI
29	Sun J, Chen LJ, Zhang GB, et al: Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma. Cancer Immunol Immunother. 59:1163–1171. 2010. View Article : Google Scholar : PubMed/NCBI
30	Zhou GX, Ireland J, Rayman P, et al: Quantification of carbonic anhydrase IX expression in serum and tissue of renal cell carcinoma patients using enzyme-linked immunosorbent assay: prognostic and diagnostic potentials. Urology. 75:257–261. 2010. View Article : Google Scholar
31	Yang QS, Gu JL, Du LQ, et al: ShRNA-mediated Ku80 gene silencing inhibits cell proliferation and sensitizes to gamma-radiation and mitomycin C-induced apoptosis in esophageal squamous cell carcinoma lines. J Radiat Res. 49:399–407. 2008. View Article : Google Scholar : PubMed/NCBI