Synthetic small peptides acting on B7H1 enhance apoptosis in pancreatic cancer cells

Wang,Fan; Ma,Jun; Liu,Junwei; Jin,Hongchuan; Huang,Dongsheng

doi:10.3892/mmr.2012.970

September 2012 Volume 6 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

September 2012 Volume 6 Issue 3

Full Size Image

Article

Synthetic small peptides acting on B7H1 enhance apoptosis in pancreatic cancer cells

Authors:
- Fan Wang
- Jun Ma
- Junwei Liu
- Hongchuan Jin
- Dongsheng Huang
View Affiliations / Copyright

Affiliations: Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China, Biomedical Research Center, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China
Pages: 553-557
|
Published online on: June 27, 2012

https://doi.org/10.3892/mmr.2012.970
Expand metrics +

Abstract

The interaction of B7H1 in tumor cells with programmed death-1 (PD-1) in T cells plays an important role in the suppression of immune responses. However, the effects of the expression of B7H1 and the PD-1/programmed death 1 ligand 1 (PD-L1) complex on tumor cells themselves remain largely unknown. In order to clarify this, we induced apoptosis in a number of human pancreatic cancer cells with different expression levels of B7H1 and designed small peptides to interfere with the function of B7H1. In this study, we chose 2 human pancreatic cancer cell lines (BxPC-3 and Panc-1 cells). Cells with a high expression of B7H1 (BxPC-3 cells and Panc-1 cells treated with interferon-γ) presented much lower levels of drug-induced apoptosis after they were incubated with PD-1 immunoglobulin. Furthermore, the percentage of BxPC-3 apoptotic cells transfected with B7H1 siRNA was higher compared to that of cells transfected with control siRNA. Both of these results indicate that the PD-1/PD-L1 complex transfers a reverse signal to B7H1+ pancreatic cancer cells upon drug-induced apoptosis in vitro. This effect may be a substantial factor for drug resistance during antitumor therapies. However, synthetic small peptides designed according to the amino acid residues of the PD-1/PD-L1 complex interrupt this effect successfully by their binding to cell membranes and acting like a blocking agent. This result may lead to a breakthrough in pancreatic cancer treatment.

View Figures

View References

1	Lowenfels AB and Maisonneuve P: Epidemiology and risk factors for pancreatic cancer. Best Pract Res Clin Gastroenterol. 20:197–209. 2006. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2007. CA Cancer J Clin. 57:43–66. 2007. View Article : Google Scholar
3	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar
4	Merl MY, Li J and Saif MW: The first-line treatment for advanced pancreatic cancer. In: Highlights from the ‘2010 ASCO Gastrointestinal Cancers Symposium’; Orlando, FL, USA. January 22–24, 2010; JOP. 11. pp. 148–150. 2010, PubMed/NCBI
5	Dong H, Zhu G, Tamada K, et al: B7-H1, a third member of the B7 family, costimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 5:1365–1369. 1999. View Article : Google Scholar : PubMed/NCBI
6	Nomi T, Sho M, Akahori T, et al: Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 13:2151–2157. 2007. View Article : Google Scholar : PubMed/NCBI
7	Liu SM, Meng Q, Zhang QX, et al: Expression and significance of B7-H1 and its receptor PD-1 in human gastric carcinoma. Zhonghua Zhong Liu Za Zhi. 30:192–195. 2008.PubMed/NCBI
8	Ohigashi Y, Sho M, Yamada Y, et al: Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res. 11:2947–2953. 2005. View Article : Google Scholar : PubMed/NCBI
9	Chen L: Coinhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol. 4:336–347. 2004. View Article : Google Scholar : PubMed/NCBI
10	David Y, Yoshimasa T, Masashi I, et al: The PD-1/PD-L1 complex resembles the antigen-binding Fv domains of antibodies and T cell receptors. PNAS. 105:3011–3016. 2008. View Article : Google Scholar : PubMed/NCBI
11	Hirano F, Kaneko K, Tamura H, et al: Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res. 65:1089–1096. 2005.PubMed/NCBI
12	Dong H, Strome SE, Salomao DR, et al: Tumor associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 8:793–800. 2002. View Article : Google Scholar : PubMed/NCBI
13	Okazaki T and Honjo T: The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 27:195–201. 2006. View Article : Google Scholar : PubMed/NCBI
14	Iwai Y, Ishida M, Tanaka Y, et al: Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 99:12293–12297. 2002. View Article : Google Scholar : PubMed/NCBI
15	Blank C, Brown I, Peterson AC, et al: PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8⁺ T cells. Cancer Res. 64:1140–1145. 2004. View Article : Google Scholar : PubMed/NCBI
16	Latchman YE, Liang SC, Wu Y, et al: PD-L1-deficient mice show that PD-L1 on T cells, antigen presenting cells, and host tissues negatively regulates T cells. Proc Natl Acad Sci USA. 101:10691–10696. 2004. View Article : Google Scholar : PubMed/NCBI
17	Hanahan D and Weinberg RA: Hallmarks of cancer: the next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
18	Ghebeh H, Lehe C, Barhoush E, et al: Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule. Breast Cancer Res. 12:R482010. View Article : Google Scholar : PubMed/NCBI
19	Azuma T, Yao S, Zhu G, et al: B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells. Blood. 111:3635–3643. 2008. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Synthetic small peptides acting on B7H1 enhance apoptosis in pancreatic cancer cells

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles