Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Medical Oncology
Published in: Medical Oncology 1/2012

01-03-2012 | Original Paper

Down-regulation of vascular endothelial growth factor expression by anti-her2/neu single chain antibodies

Authors: Foroogh Nejatollahi, Mahdi Asgharpour, Mansooreh Jaberipour

Published in: Medical Oncology | Issue 1/2012

Login to get access

Abstract

HER-2/neu is overexpressed in 25–30% of breast tumors. Signaling through HER-2/neu leads to an increase in the production of vascular endothelial growth factor (VEGF) and enhances angiogenesis. We evaluated the effects of three specific anti-HER2/neu single chain-Fv (scFv) antibodies on the expression level of VEGF in HER2/neu-expressing breast cancer cell lines. A nonimmunized human scFv library was panned against three epitopes of HER2/neu. BT-474 human breast cancer cell line was treated with three specific anti-HER2/neu scFv antibodies and the amount of VEGF gene transcript was determined by quantitative real-time PCR. The expression of VEGF protein was analyzed by western blot. All three scFv antibodies along with their combination inhibited VEGF expression at both the gene and protein levels. Our results show that anti-HER2/neu recombinant antibodies can be considered as anti-angiogenic agents in HER2/neu-positive breast cancers.
Literature
1.
Hung MC, Lau YK. Basic science of HER-2/neu: a review. Semin Oncol. (1999);26(4 Suppl 12):51–9.
2.
3.
Natali PG, et al. Expression of the p185 encoded by HER2 oncogene in normal and transformed human tissues. Int J Cancer. 1990;45(3):457–61.PubMedCrossRef
4.
Brennan PJ, et al. HER2/Neu: mechanisms of dimerization/oligomerization. Oncogene. (2002);21(2):328.
5.
Zaczek A, Brandt B, Bielawski KP. The diverse signaling network of EGFR, HER2, HER3 and HER4 tyrosine kinase receptors and the consequences for therapeutic approaches. Histol Histopathol. 2005;20(3):1005–15.PubMed
6.
Harari D, Yarden Y. Molecular mechanisms underlying ErbB2/HER2 action in breast cancer. Oncogene. 2000;19(53):6102–14.PubMedCrossRef
7.
Zhou BP, Hung MC. Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin Oncol. (2003);30(5 Suppl 16):38–48.
8.
Petit AM, et al. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol. 1997;151(6):1523–30.PubMed
9.
Ferrara N. Role of vascular endothelial growth factor in regulation of physiological angiogenesis. Am J Physiol Cell Physiol. 2001;280(6):C1358–66.PubMed
10.
Gupta K, et al. VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp Cell Res. 1999;247(2):495–504.PubMedCrossRef
11.
Pidgeon GP, et al. Vascular endothelial growth factor (VEGF) upregulates BCL-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells. Br J Cancer. 2001;85(2):273–8.PubMedCrossRef
12.
Tran J, et al. Marked induction of the IAP family antiapoptotic proteins survivin and XIAP by VEGF in vascular endothelial cells. Biochem Biophys Res Commun. 1999;264(3):781–8.PubMedCrossRef
13.
Zachary I. Signaling mechanisms mediating vascular protective actions of vascular endothelial growth factor. Am J Physiol Cell Physiol. 2001;280(6):C1375–86.PubMed
14.
Weis SM, Cheresh DA. Pathophysiological consequences of VEGF-induced vascular permeability. Nature. 2005;437(7058):497–504.PubMedCrossRef
15.
JP ShepardHM, Slamon DJ, Pirot Z, Maneval DC. Herceptin. Handb Exp Pharmacol. 2008;181:183–219.CrossRef
16.
FDA expands us of herceptin for early-stage breast cancer. Mayo Clin Womens Healthsource. 2007;11(6):3.
17.
Burris H 3rd, et al. Phase II trial of trastuzumab followed by weekly paclitaxel/carboplatin as first-line treatment for patients with metastatic breast cancer. J Clin Oncol. 2004;22(9):1621–9.PubMedCrossRef
18.
Vogel CL, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2002;20(3):719–26.PubMedCrossRef
19.
Nielsen DL, Andersson M, Kamby C. HER2-targeted therapy in breast cancer. Monoclonal antibodies and tyrosine kinase inhibitors. Cancer Treat Rev. 2009;35(2):121–36.PubMedCrossRef
20.
Metzger Filho O, Saini KS, Azim HA, Jr., Awada A (2010)Prevention and management of major side effects of targeted agents in breast cancer. Crit Rev Oncol Hematol.
21.
Du XL, Xia R, Burau K, Liu CC (2010)Cardiac risk associated with the receipt of anthracycline and trastuzumab in a large nationwide cohort of older women with breast cancer, 1998–2005. Med Oncol.
22.
Orphanos GS, Ioannidis GN, Ardavanis AG. Cardiotoxicity induced by tyrosine kinase inhibitors. Acta Oncol. 2009;48(7):964–70.PubMedCrossRef
23.
Nuttall SD, Irving RA, Hudson PJ. Immunoglobulin VH domains and beyond: design and selection of single-domain binding and targeting reagents. Curr Pharm Biotechnol. 2000;1(3):253–63.PubMedCrossRef
24.
Batra SK, et al. Pharmacokinetics and biodistribution of genetically engineered antibodies. Curr Opin Biotechnol. 2002;13(6):603–8.PubMedCrossRef
25.
Curigliano G, et al. Cardiac toxicity from systemic cancer therapy: a comprehensive review. Prog Cardiovasc Dis. 2010;53(2):94–104.PubMedCrossRef
26.
Nejatollahi F, Hodgetts SJ, Vallely PJ, Burnie JP. Neutralising human recombinant antibodies to human cytomegalovirus glycoproteins gB and gH. FEMS Immunol Med Microbiol. 2002;34(3):237–44.PubMedCrossRef
27.
Nahta R, Esteva FJ. In vitro effects of trastuzumab and vinorelbine in trastuzumab-resistant breast cancer cells. Cancer Chemother Pharmacol. 2004;53:186–90.PubMedCrossRef
28.
Kern FG, Lippman ME. The role of angiogenic growth factors in breast cancer progression. Cancer Metastasis Rev. 1996;15(2):213–9.PubMedCrossRef
29.
Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis–correlation in invasive breast carcinoma. N Engl J Med. 1991;324(1):1–8.PubMedCrossRef
30.
Folkman J, D’Amore PA. Blood vessel formation: what is its molecular basis? Cell. 1996;87(7):1153–5.PubMedCrossRef
31.
Thomas KA. Vascular endothelial growth factor, a potent and selective angiogenic agent. J Biol Chem. 1996;271(2):603–6.PubMed
32.
Foekens JA, et al. High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer. Cancer Res. 2001;61(14):5407–14.PubMed
33.
Gasparini G. Prognostic value of vascular endothelial growth factor in breast cancer. Oncologist. (2000);5 Suppl 1: 37–44.
34.
Konecny GE, et al. Association between HER-2/neu and vascular endothelial growth factor expression predicts clinical outcome in primary breast cancer patients. Clin Cancer Res. 2004;10(5):1706–16.PubMedCrossRef
35.
Schoppmann SF, et al. HER2/neu expression correlates with vascular endothelial growth factor-C and lymphangiogenesis in lymph node-positive breast cancer. Ann Oncol. 2010;21(5):955–60.PubMedCrossRef
36.
Linderholm B, et al. Overexpression of c-erbB-2 is related to a higher expression of vascular endothelial growth factor (VEGF) and constitutes an independent prognostic factor in primary node-positive breast cancer after adjuvant systemic treatment. Eur J Cancer. 2004;40(1):33–42.PubMedCrossRef
37.
Loureiro RM, et al. ErbB2 overexpression in mammary cells upregulates VEGF through the core promoter. Biochem Biophys Res Commun. 2005;326(2):455–65.PubMedCrossRef
38.
Pegram MD, Reese DM. Combined biological therapy of breast cancer using monoclonal antibodies directed against HER2/neu protein and vascular endothelial growth factor. Semin Oncol. (2002);29(3 Suppl 11):29–37.
39.
Yen L, et al. Differential regulation of tumor angiogenesis by distinct ErbB homo—and heterodimers. Mol Biol Cell. 2002;13(11):4029–44.PubMedCrossRef
40.
Wen XF, et al. HER2 signaling modulates the equilibrium between pro—and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy. Oncogene. 2006;25(52):6986–96.PubMedCrossRef
41.
Scott LJ. Bevacizumab: in first-line treatment of metastatic breast cancer. Drugs. 2007;67(12):1793–9.PubMedCrossRef
42.
Yen L, et al. Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene. 2000;19(31):3460–9.PubMedCrossRef
43.
Montgomery RB, et al. Endogenous anti-HER2 antibodies block HER2 phosphorylation and signaling through extracellular signal-regulated kinase. Cancer Res. 2005;65(2):650–6.PubMed
Metadata
Title
Down-regulation of vascular endothelial growth factor expression by anti-her2/neu single chain antibodies
Authors
Foroogh Nejatollahi
Mahdi Asgharpour
Mansooreh Jaberipour
Publication date
01-03-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 1/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-010-9796-5

Other articles of this Issue 1/2012

Medical Oncology 1/2012 Go to the issue

Original Paper

Gemcitabine and cisplatin combination regimen in patients with anthracycline- and taxane-pretreated metastatic breast cancer

Original Paper

Clinical prognostic analysis of 116 patients with primary intestinal non-Hodgkin lymphoma

Original paper

Interleukin-8 is associated with adhesion, migration and invasion in human gastric cancer SCG-7901 cells

Original paper

Chemotherapy with PLGA microspheres containing docetaxel decreases angiogenesis in human hepatoma xenograft

Original Paper

Vasculogenic mimicry–potential target for glioblastoma therapy: an in vitro and in vivo study

Original Paper

Significance of pretreatment comorbidities in elderly patients with advanced non-small-cell lung cancer treated with chemotherapy or epidermal growth factor receptor-tyrosine kinase inhibitor
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits