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
Pathology & Oncology Research
Published in: Pathology & Oncology Research 4/2012

Open Access 01-10-2012 | Research

Angiotensin II Type 1 Receptor (AT-1R) Expression Correlates with VEGF-A and VEGF-D Expression in Invasive Ductal Breast Cancer

Authors: Aleksandra Jethon, Bartosz Pula, Aleksandra Piotrowska, Andrzej Wojnar, Janusz Rys, Piotr Dziegiel, Marzena Podhorska-Okolow

Published in: Pathology & Oncology Research | Issue 4/2012

Login to get access

Abstract

Recent studies point to the involvement of angiotensin II (Ang II) receptor type 1 (AT-1R) on processes of metastasing, stimulation of invasiveness and angiogenesis in tumours. In this study, the correlation between intensity of AT-1R expression and expression of lymph- and angiogenesis markers in invasive ductal breast cancers (IDC) was examined. Immunohistochemical studies (IHC) were performed on archival material of 102 IDC cases. Only 28 (27.5%) cases manifested low AT-1R expression while 74 (72.5%) cases demonstrated a moderate or pronounced AT-1R expression. Expression intensity of AT-1R was found to correlate with expressions of VEGF-A (r = 0.26; p = 0.008) and VEGF-D (r = 0.24; p = 0.015). Out of the examined markers of angiogenesis and lymphangiogenesis only the pronounced expression of VEGF-C was found to correlate with patient poor clinical outcome (p = 0.009). The positive correlation between AT-1R and VEGF-A and VEGF-D could point to stimulatory action of Ang II on their expression what might result in augmented lymph- and angiogenesis in IDC.
Literature
1.
Ferlay J, Shin H-R, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917PubMedCrossRef
2.
3.
Chappell M (2010) Angiotensin-converting enzyme 2 autoantibodies: further evidence for a role of the renin-angiotensin system in inflammation. Arthritis Res Ther 12:128PubMedCrossRef
4.
De Paepe B, Verstraeten VL, De Potter CR, Vakaet LA, Bullock GR (2001) Growth stimulatory angiotensin II type-1 receptor is upregulated in breast hyperplasia and in situ carcinoma but not in invasive carcinoma. Histochem Cell Biol 116:247–254PubMed
5.
De Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T (2000) International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev 52:415–472PubMed
6.
Gwathmey TM, Shaltout HA, Pendergrass KD, Pirro NT, Figueroa JP, Rose JC, Diz DI, Chappell MC (2009) Nuclear angiotensin II type 2 (AT2) receptors are functionally linked to nitric oxide production. Am J Physiol Renal Physiol 296:1484–1493CrossRef
7.
Muscella A, Greco S, Elia MG, Storelli C, Marsigliante S (2002) Angiotensin II stimulation of Na+/K + ATPase activity and cell growth by calcium-independent pathway in MCF-7 breast cancer cells. J Endocrinol 173:315–323PubMedCrossRef
8.
Tahmasebi M, Barker S, Puddefoot JR, Vinson GP (2006) Localisation of renin-angiotensin system (RAS) components in breast. Br J Cancer 95:67–74PubMedCrossRef
9.
Steckelings UM, Kaschina E, Unger T (2005) The AT2 receptor—a matter of love and hate. Peptides 26:1401–1409PubMedCrossRef
10.
Bonnet F, Cao Z, Cooper ME (2001) Apoptosis and angiotensin II: yet another renal regulatory system? Exp Nephrol 9:295–300PubMedCrossRef
11.
Deshayes F, Nahmias C (2005) Angiotensin receptors: a new role in cancer? Trends Endocrinol Metabol 16:293–299CrossRef
12.
Fujimoto Y, Sasaki T, Tsuchida A, Chayama K (2001) Angiotensin II type 1 receptor expression in human pancreatic cancer and growth inhibition by angiotensin II type 1 receptor antagonist. FEBS Letters 495:197–200PubMedCrossRef
13.
Goldfarb DA, Diz DI, Tubbs RR, Ferrario CM, Novick AC (1994) Angiotensin II receptor subtypes in the human renal cortex and renal cell carcinoma. J Urol 151:208–213PubMed
14.
Batra VK, Gopalakrishnan V, McNeill JR, Hickie RA (1994) Angiotensin II elevates cytosolic free calcium in human lung adenocarcinoma cells via activation of AT1 receptors. Cancer Lett 76:19–24PubMedCrossRef
15.
Inwang ER, Puddefoot JR, Brown CL, Goode AW, Marsigliante S, Ho MM, Payne JG, Vinson GP (1997) Angiotensin II type 1 receptor expression in human breast tissues. Br J Cancer 75:1279–1283PubMedCrossRef
16.
Greco S, Elia MG, Muscella A, Storelli C, Marsigliante S (2002) AT1 angiotensin II receptor mediates intracellular calcium mobilization in normal and cancerous breast cells in primary culture. Cell Calcium 32:1–10PubMedCrossRef
17.
Suzuki Y, Ruiz-Ortega M, Lorenzo O, Ruperez M, Esteban V, Egido J (2003) Inflammation and angiotensin II. Int J Biochem Cell Biol 35:881–900PubMedCrossRef
18.
Puddefoot JR, Udeozo UK, Barker S, Vinson GP (2006) The role of angiotensin II in the regulation of breast cancer cell adhesion and invasion. Endocr Relat Cancer 13:895–903PubMedCrossRef
19.
Herr D, Rodewald M, Fraser HM, Hack G, Konrad R, Kreienberg R, Wulff C (2008) Potential role of Renin-Angiotensin-system for tumor angiogenesis in receptor negative breast cancer. Gynecol Oncol 109:418–425PubMedCrossRef
20.
Suganuma T, Ino K, Shibata K, Kajiyama H, Nagasaka T, Mizutani S, Kikkawa F (2005) Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma cells and its blockade therapy resulting in suppression of tumor invasion, angiogenesis, and peritoneal dissemination. Clin Cancer Res 11:2686–2694PubMedCrossRef
21.
Khakoo AY, Sidman RL, Pasqualini R, Arap W (2008) Does the renin-angiotensin system participate in regulation of human vasculogenesis and angiogenesis? Cancer Res 68:9112–9115PubMedCrossRef
22.
Fox SB, Gasparini G, Harris AL (2001) Angiogenesis: pathological, prognostic, and growth-factor pathways and their link to trial design and anticancer drugs. Lancet Oncol 2:278–289PubMedCrossRef
23.
Imanishi T, Hano T, Nishio I (2004) Angiotensin II potentiates vascular endothelial growth factor-induced proliferation and network formation of endothelial progenitor cells. Hypertens Res 27:101–108PubMedCrossRef
24.
Wasa J, Sugiura H, Kozawa E, Kohyama K, Yamada K, Taguchi O (2011) The tumor suppressive effect of angiotensin II type 1 receptor antagonist in a murine osteosarcoma model. Anticancer Res 31:123–127PubMed
25.
Gomulkiewicz A, Podhorska-Okolow M, Szulc R, Smorag Z, Wojnar A, Zabel M, Dziegiel P (2010) Correlation between metallothionein (MT) expression and selected prognostic factors in ductal breast cancers. Folia Histochem Cytobiol 48:242–248PubMedCrossRef
26.
Remmele W, Stegner HE (1987) Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe 8:138–40PubMed
27.
Willis LM, El-Remessy AB, Somanath PR, Deremer DL, Fagan SC (2011) Angiotensin receptor blockers and angiogenesis: clinical and experimental evidence. Clin Sci 120:307–319PubMedCrossRef
28.
Greco S, Muscella A, Elia MG, Salvatore P, Storelli C, Marsigliante S (2002) Activation of angiotensin II type I receptor promotes protein kinase C translocation and cell proliferation in human cultured breast epithelial cells. J Endocrinol 174:205–214PubMedCrossRef
29.
Rhodes DR, Ateeq B, Cao Q, Tomlins SA, Mehra R, Laxman B, Kalyana-Sundaram S, Lonigro RJ, Helgeson BE, Bhojani MS, Rehemtulla A, Kleer CG, Hayes DF, Lucas PC, Varambally S, Chinnaiyan AM (2009) AGTR1 overexpression defines a subset of breast cancer and confers sensitivity to losartan, an AGTR1 antagonist. Proc Natl Acad Sci U S A 106:10284–10289PubMedCrossRef
30.
Kosugi M, Miyajima A, Kikuchi E, Kosaka T, Horiguchi Y, Murai M (2007) Effect of angiotensin II type 1 receptor antagonist on tumor growth and angiogenesis in a xenograft model of human bladder cancer. Human Cell 20:1–9PubMedCrossRef
31.
Imai N, Hashimoto T, Kihara M, Yoshida S, Kawana I, Yazawa T, Kitamura H, Umemura S (2006) Roles for host and tumor angiotensin II type 1 receptor in tumor growth and tumor-associated angiogenesis. Lab Invest 87:189–198PubMedCrossRef
32.
Fujita M, Hayashi I, Yamashina S, Fukamizu A, Itoman M, Majima M (2005) Angiotensin type 1a receptor signaling-dependent induction of vascular endothelial growth factor in stroma is relevant to tumor-associated angiogenesis and tumor growth. Carcinogenesis 26:271–279PubMedCrossRef
33.
Noguchi R, Yoshiji H, Ikenaka Y, Namisaki T, Kitade M, Kaji K, Yoshii J, Yanase K, Yamazaki M, Tsujimoto T, Kawaratani H, Fukui H (2009) Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic activities. Oncol Rep 22:355–360PubMed
34.
Gu Y, Qi X, Guo S (2008) Lymphangiogenesis induced by VEGF-C and VEGF-D promotes metastasis and a poor outcome in breast carcinoma: a retrospective study of 61 cases. Clin Exp Metastasis 25:717–725PubMedCrossRef
35.
Mohammed RAA, Green A, El-Shikh S, Paish EC, Ellis IO, Martin SG (2007) Prognostic significance of vascular endothelial cell growth factors -A, -C and -D in breast cancer and their relationship with angio- and lymphangiogenesis. Br J Cancer 96:1092–1100PubMedCrossRef
36.
Mylona E, Nomikos A, Alexandrou P, Giannopoulou I, Keramopoulos A, Nakopoulou L (2007) Lymphatic and blood vessel morphometry in invasive breast carcinomas: relation with proliferation and VEGF-C and -D proteins expression. Histol Histopathol 22:825–835PubMed
37.
Gisterek I, Matkowski R, Koźlak J, Duś D, Łacko A, Szelachowska J, Kornafel J (2007) Evaluation of prognostic value of VEGF-C and VEGF-D in breast cancer - 10 years follow-up analysis. Anticancer Res 27:2797–2802PubMed
38.
Mylona E, Alexandrou P, Mpakali A, Giannopoulou I, Liapis G, Markaki S, Keramopoulos A, Nakopoulou L (2007) Clinicopathological and prognostic significance of vascular endothelial growth factors (VEGF)-C and -D and VEGF receptor 3 in invasive breast carcinoma. Eur J Surg Oncol 33:294–300PubMedCrossRef
39.
van der Schaft DWJ, Pauwels P, Hulsmans S, Zimmermann M, van de Poll-Franse LV, Griffioen AW (2007) Absence of lymphangiogenesis in ductal breast cancer at the primary tumor site. Cancer Lett 254:128–136PubMedCrossRef
40.
Orimo A, Gupta PB, Sgroi DC, Arenzana-Seisdedos F, Delaunay T, Naeem R, Carey VJ, Richardson AL, Weinberg RA (2005) Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 121:335–348PubMedCrossRef
41.
Eubank TD, Roberts RD, Khan M, Curry JM, Nuovo GJ, Kuppusamy P, Marsh CB (2009) Granulocyte macrophage colony-stimulating factor inhibits breast cancer growth and metastasis by invoking an anti-angiogenic program in tumor-educated macrophages. Cancer Res 69:2133–2140PubMedCrossRef
42.
Joimel U, Gest C, Soria J, Pritchard LL, Alexandre J, Laurent M, Blot E, Cazin L, Vannier JP, Varin R, Li H, Soria C (2010) Stimulation of angiogenesis resulting from cooperation between macrophages and MDA-MB-231 breast cancer cells: proposed molecular mechanism and effect of tetrathiomolybdate. BMC Cancer 10:375PubMedCrossRef
43.
Lambert DW, Clarke NE, Turner AJ (2010) Not just angiotensinases: new roles for the angiotensin-converting enzymes. Cell Mol Life Sci 67:89–98PubMedCrossRef
44.
González-Zuloeta Ladd AM, Arias Vásquez A, Sayed-Tabatabaei FA, Coebergh JW, Hofman A, Njajou O, Stricker B, van Duijn C (2005) Angiotensin-converting enzyme gene insertion/deletion polymorphism and breast cancer risk. Cancer Epidemiol Biomarkers Prev 14:2143–2146PubMedCrossRef
45.
González-Zuloeta Ladd AM, Arias Vásquez A, Siemes C, Yazdanpanah M, Coebergh JW, Hofman A, Stricker BH, van Duijn CM (2007) Differential roles of angiotensinogen and angiotensin receptor type 1 polymorphisms in breast cancer risk. Breast Cancer Res Treat 10:299–304
Metadata
Title
Angiotensin II Type 1 Receptor (AT-1R) Expression Correlates with VEGF-A and VEGF-D Expression in Invasive Ductal Breast Cancer
Authors
Aleksandra Jethon
Bartosz Pula
Aleksandra Piotrowska
Andrzej Wojnar
Janusz Rys
Piotr Dziegiel
Marzena Podhorska-Okolow
Publication date
01-10-2012
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 4/2012
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-012-9516-x

Other articles of this Issue 4/2012

Pathology & Oncology Research 4/2012 Go to the issue

Research

Activated Platelets Interact with Lung Cancer Cells Through P-Selectin Glycoprotein Ligand-1

Research

Contribution of IL12A and IL12B Polymorphisms to the Risk of Cervical Cancer

Research

Expression Pattern and Prognostic Significance of IGFBP Isoforms in Anaplastic Astrocytoma

Research

Expression of High Mobility GroupA2 is Associated with Poor Survival in Hepatocellular Carcinoma

Research

Expression of BAG-1 and PARP-1 in Precursor Lesions and Invasive Cervical Cancer Associated with Human Papillomavirus (HPV)

Research

Genetic Polymorphism of XRCC1 Correlated with Response to Oxaliplatin-Based Chemotherapy in Advanced Colorectal Cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits