Next Article in Journal
LXXLL Peptide Converts Transportan 10 to a Potent Inducer of Apoptosis in Breast Cancer Cells
Next Article in Special Issue
Treatment of Single or Multiple Brain Metastases by Hypofractionated Stereotactic Radiotherapy Using Helical Tomotherapy
Previous Article in Journal
Effects of Lipoic Acid on Immune Function, the Antioxidant Defense System, and Inflammation-Related Genes Expression of Broiler Chickens Fed Aflatoxin Contaminated Diets
Previous Article in Special Issue
Surgical Resection of Brain Metastases—Impact on Neurological Outcome
Open AccessArticle

Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy?

Department of Human Pathology "G. Barresi", University of Messina, Messina 98125, Italy
Department of Neurosciences, University of Messina, Messina 98125, Italy
Department G.F. Ingrassia, Section of Anatomic Pathology, University of Catania, Catania 95123, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2014, 15(4), 5663-5679;
Received: 20 January 2014 / Revised: 10 March 2014 / Accepted: 25 March 2014 / Published: 2 April 2014
(This article belongs to the Special Issue Brain Metastasis 2014)
Despite ongoing clinical trials, the efficacy of anti-angiogenic drugs for the treatment of brain metastases (BM) is still questionable. The lower response rate to anti-angiogenic therapy in the presence of BM than in metastatic disease involving other sites suggests that BM may be insensitive to these drugs, although the biological reasons underlining this phenomenon are still to be clarified. With the aim of assessing whether the targets of anti-angiogenic therapies are actually present in BM, in the present study, we analyzed the microvessel density (MVD), a measure of neo-angiogenesis, and the vascular phenotype (mature vs. immature) in the tumor tissue of a series of BM derived from different primary tumors. By using immunohistochemistry against endoglin, a specific marker for newly formed vessels, we found that neo-angiogenesis widely varies in BM depending on the site of the primary tumor, as well as on its histotype. According to our results, BM from lung cancer displayed the highest MVD counts, while those from renal carcinoma had the lowest. Then, among BM from lung cancer, those from large cell and adenocarcinoma histotypes had significantly higher MVD counts than those originating from squamous cell carcinoma (p = 0.0043; p = 0.0063). Of note, MVD counts were inversely correlated with the maturation index of the endoglin-stained vessels, reflected by the coverage of smooth muscle actin (SMA) positive pericytes (r = −0.693; p < 0.0001). Accordingly, all the endoglin-positive vessels in BM from pulmonary squamous cell carcinoma and renal carcinoma, displayed a mature phenotype, while vessels with an immature phenotype were found in highly vascularized BM from pulmonary large cell and adenocarcinoma. The low MVD and mature phenotype observed in BM from some primary tumors may account for their low sensitivity to anti-angiogenic therapies. Although our findings need to be validated in correlative studies with a clinical response, this should be taken into account in therapeutic protocols in order to avoid the adverse effects of useless therapies. View Full-Text
Keywords: brain metastasis; endoglin; MVD; pericytes; angiogenesis brain metastasis; endoglin; MVD; pericytes; angiogenesis
MDPI and ACS Style

Barresi, V.; Branca, G.; Caffo, M.; Caltabiano, R.; Ieni, A.; Vitarelli, E.; Lanzafame, S.; Tuccari, G. Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? Int. J. Mol. Sci. 2014, 15, 5663-5679.

Show more citation formats Show less citations formats

Article Access Map by Country/Region

Only visits after 24 November 2015 are recorded.
Back to TopTop