Cargando…

Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion

Tumor- or cancer-associated fibroblasts (TAFs or CAFs) are active players in tumorigenesis and exhibit distinct angiogenic and tumorigenic properties. Adrenomedullin (AM), a multifunctional peptide plays an important role in angiogenesis and tumor growth through its receptors calcitonin receptor-lik...

Descripción completa

Detalles Bibliográficos
Autores principales: Benyahia, Zohra, Dussault, Nadège, Cayol, Mylène, Sigaud, Romain, Berenguer-Daizé, Caroline, Delfino, Christine, Tounsi, Asma, Garcia, Stéphane, Martin, Pierre-Marie, Mabrouk, Kamel, Ouafik, L’Houcine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362520/
https://www.ncbi.nlm.nih.gov/pubmed/28178651
http://dx.doi.org/10.18632/oncotarget.14999
_version_ 1782516968772861952
author Benyahia, Zohra
Dussault, Nadège
Cayol, Mylène
Sigaud, Romain
Berenguer-Daizé, Caroline
Delfino, Christine
Tounsi, Asma
Garcia, Stéphane
Martin, Pierre-Marie
Mabrouk, Kamel
Ouafik, L’Houcine
author_facet Benyahia, Zohra
Dussault, Nadège
Cayol, Mylène
Sigaud, Romain
Berenguer-Daizé, Caroline
Delfino, Christine
Tounsi, Asma
Garcia, Stéphane
Martin, Pierre-Marie
Mabrouk, Kamel
Ouafik, L’Houcine
author_sort Benyahia, Zohra
collection PubMed
description Tumor- or cancer-associated fibroblasts (TAFs or CAFs) are active players in tumorigenesis and exhibit distinct angiogenic and tumorigenic properties. Adrenomedullin (AM), a multifunctional peptide plays an important role in angiogenesis and tumor growth through its receptors calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). We show that AM and AM receptors mRNAs are highly expressed in CAFs prepared from invasive breast carcinoma when compared to normal fibroblasts. Immunostaining demonstrates the presence of immunoreactive AM and AM receptors in the CAFs (n = 9). The proliferation of CAFs is decreased by anti-AM antibody (αAM) and anti-AM receptors antibody (αAMR) treatment, suggesting that AM may function as a potent autocrine/paracrine growth factor. Systemic administration of αAMR reduced neovascularization of in vivo Matrigel plugs containing CAFs as demonstrated by reduced numbers of the vessel structures, suggesting that AM is one of the CAFs-derived factors responsible for endothelial cell-like and pericytes recruitment to built a neovascularization. We show that MCF-7 admixed with CAFs generated tumors of greater volume significantly different from the MCF-7 xenografts in nude mice due in part to the induced angiogenesis. αAMR and AM(22-52) therapies significantly suppressed the growth of CAFs/MCF-7 tumors. Histological examination of tumors treated with AM(22-52) and aAMR showed evidence of disruption of tumor vasculature with depletion of vascular endothelial cells, induced apoptosis and decrease of tumor cell proliferation. Our findings highlight the importance of CAFs-derived AM pathway in growth of breast carcinoma and in neovascularization by supplying and amplifying signals that are essential for pathologic angiogenesis.
format Online
Article
Text
id pubmed-5362520
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-53625202017-04-24 Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion Benyahia, Zohra Dussault, Nadège Cayol, Mylène Sigaud, Romain Berenguer-Daizé, Caroline Delfino, Christine Tounsi, Asma Garcia, Stéphane Martin, Pierre-Marie Mabrouk, Kamel Ouafik, L’Houcine Oncotarget Research Paper Tumor- or cancer-associated fibroblasts (TAFs or CAFs) are active players in tumorigenesis and exhibit distinct angiogenic and tumorigenic properties. Adrenomedullin (AM), a multifunctional peptide plays an important role in angiogenesis and tumor growth through its receptors calcitonin receptor-like receptor/receptor activity modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). We show that AM and AM receptors mRNAs are highly expressed in CAFs prepared from invasive breast carcinoma when compared to normal fibroblasts. Immunostaining demonstrates the presence of immunoreactive AM and AM receptors in the CAFs (n = 9). The proliferation of CAFs is decreased by anti-AM antibody (αAM) and anti-AM receptors antibody (αAMR) treatment, suggesting that AM may function as a potent autocrine/paracrine growth factor. Systemic administration of αAMR reduced neovascularization of in vivo Matrigel plugs containing CAFs as demonstrated by reduced numbers of the vessel structures, suggesting that AM is one of the CAFs-derived factors responsible for endothelial cell-like and pericytes recruitment to built a neovascularization. We show that MCF-7 admixed with CAFs generated tumors of greater volume significantly different from the MCF-7 xenografts in nude mice due in part to the induced angiogenesis. αAMR and AM(22-52) therapies significantly suppressed the growth of CAFs/MCF-7 tumors. Histological examination of tumors treated with AM(22-52) and aAMR showed evidence of disruption of tumor vasculature with depletion of vascular endothelial cells, induced apoptosis and decrease of tumor cell proliferation. Our findings highlight the importance of CAFs-derived AM pathway in growth of breast carcinoma and in neovascularization by supplying and amplifying signals that are essential for pathologic angiogenesis. Impact Journals LLC 2017-02-02 /pmc/articles/PMC5362520/ /pubmed/28178651 http://dx.doi.org/10.18632/oncotarget.14999 Text en Copyright: © 2017 Benyahia et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Benyahia, Zohra
Dussault, Nadège
Cayol, Mylène
Sigaud, Romain
Berenguer-Daizé, Caroline
Delfino, Christine
Tounsi, Asma
Garcia, Stéphane
Martin, Pierre-Marie
Mabrouk, Kamel
Ouafik, L’Houcine
Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion
title Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion
title_full Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion
title_fullStr Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion
title_full_unstemmed Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion
title_short Stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion
title_sort stromal fibroblasts present in breast carcinomas promote tumor growth and angiogenesis through adrenomedullin secretion
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5362520/
https://www.ncbi.nlm.nih.gov/pubmed/28178651
http://dx.doi.org/10.18632/oncotarget.14999
work_keys_str_mv AT benyahiazohra stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT dussaultnadege stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT cayolmylene stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT sigaudromain stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT berenguerdaizecaroline stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT delfinochristine stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT tounsiasma stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT garciastephane stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT martinpierremarie stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT mabroukkamel stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion
AT ouafiklhoucine stromalfibroblastspresentinbreastcarcinomaspromotetumorgrowthandangiogenesisthroughadrenomedullinsecretion