Cargando…
Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy?
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 th...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013588/ https://www.ncbi.nlm.nih.gov/pubmed/24699047 http://dx.doi.org/10.3390/ijms15045663 |
_version_ | 1782315079186776064 |
---|---|
author | Barresi, Valeria Branca, Giovanni Caffo, Maria Caltabiano, Rosario Ieni, Antonio Vitarelli, Enrica Lanzafame, Salvatore Tuccari, Giovanni |
author_facet | Barresi, Valeria Branca, Giovanni Caffo, Maria Caltabiano, Rosario Ieni, Antonio Vitarelli, Enrica Lanzafame, Salvatore Tuccari, Giovanni |
author_sort | Barresi, Valeria |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4013588 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-40135882014-05-08 Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? Barresi, Valeria Branca, Giovanni Caffo, Maria Caltabiano, Rosario Ieni, Antonio Vitarelli, Enrica Lanzafame, Salvatore Tuccari, Giovanni Int J Mol Sci Article 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. Molecular Diversity Preservation International (MDPI) 2014-04-02 /pmc/articles/PMC4013588/ /pubmed/24699047 http://dx.doi.org/10.3390/ijms15045663 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Barresi, Valeria Branca, Giovanni Caffo, Maria Caltabiano, Rosario Ieni, Antonio Vitarelli, Enrica Lanzafame, Salvatore Tuccari, Giovanni Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? |
title | Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? |
title_full | Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? |
title_fullStr | Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? |
title_full_unstemmed | Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? |
title_short | Immuno-Expression of Endoglin and Smooth Muscle Actin in the Vessels of Brain Metastases. Is There a Rational for Anti-Angiogenic Therapy? |
title_sort | immuno-expression of endoglin and smooth muscle actin in the vessels of brain metastases. is there a rational for anti-angiogenic therapy? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013588/ https://www.ncbi.nlm.nih.gov/pubmed/24699047 http://dx.doi.org/10.3390/ijms15045663 |
work_keys_str_mv | AT barresivaleria immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy AT brancagiovanni immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy AT caffomaria immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy AT caltabianorosario immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy AT ieniantonio immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy AT vitarellienrica immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy AT lanzafamesalvatore immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy AT tuccarigiovanni immunoexpressionofendoglinandsmoothmuscleactininthevesselsofbrainmetastasesistherearationalforantiangiogenictherapy |