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

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.

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…These results suggest that host stromal VEGF induction by AT 1 receptor is a key regulator of tumor growth and blockade of VEGF production by ARBs may be a novel therapeutic strategy against cancers (Egami et al, 2003;Fujita et al, 2005). AngII has been shown to function as a key role in neovascularization of hepatocellular carcinoma (Tamarat et al, 2002) in human breast carcinoma cells (Greco et al, 2002) as well as in invasive ductal breast cancer (Jethon et al, 2012). Both lisinopril and losartan treatment resulted in elevation in VEGF expression and angiogenesis, confirming the relationship between AT 1 receptor, VEGF, and vessel growth (Tamarat et al, 2002).…”

Association between AT1 and AT2 angiotensin II receptor expression with cell proliferation and angiogenesis in operable breast cancer

“…In breast cancer, activation of the AT1 receptor triggers numerous intracellular kinases leading to modulation of angiogenesis, cell proliferation, migration, and inflammation [16,17]. AT1 is overexpressed in a subpopulation of invasive breast cancer; ATR1 blockers have been proposed as a potential treatment for this population [18].…”

Angiotensin-converting enzyme and the tumor microenvironment: mechanisms beyond angiogenesis

“…A better understanding of the role of the peptide network of ACE in the tumor microenvironment provides further rationale for which combination therapies would be suitable, as well as which cancers would benefit from such therapies. One area worthy of further investigation is the characterization of the differential expression ACE and RAS components in specific tumor types as a potential predictor of response to ACE inhibitor use in combination therapy with appropriate, standard chemotherapy regimen (71,112,146).…”

“…The role of the RAS in angiogenesis and cellular growth has been demonstrated in several models. In vitro, angiotensin II mediates VEGF induction in a number of cell types, including mesenchymal stem cells (128), as well as primary pancreatic (4), breast (71), and endometrial cancer cells (112). Angiotensinogen and its cleaved derivatives, similar to other serpins (serine protease inhibitors) such as anti-thrombin III, possess anti-angiogenic properties (27,35).…”