Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.

Interactions occurring between malignant cells and the stromal microenvironment heavily influence tumor progression. We investigated whether this cross-talk affects some molecular and functional aspects specifically correlated with the invasive phenotype of breast tumor cells (i.e. adhesion molecule...

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Autores principales: Cristiana Angelucci, Giuseppe Maulucci, Gina Lama, Gabriella Proietti, Anna Colabianchi, Massimiliano Papi, Alessandro Maiorana, Marco De Spirito, Alessandra Micera, Omar Bijorn Balzamino, Alba Di Leone, Riccardo Masetti, Gigliola Sica
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:5ddb606713a646948b689df132d004852021-11-18T08:05:51ZEpithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.1932-620310.1371/journal.pone.0050804https://doaj.org/article/5ddb606713a646948b689df132d004852012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23251387/?tool=EBIhttps://doaj.org/toc/1932-6203Interactions occurring between malignant cells and the stromal microenvironment heavily influence tumor progression. We investigated whether this cross-talk affects some molecular and functional aspects specifically correlated with the invasive phenotype of breast tumor cells (i.e. adhesion molecule expression, membrane fluidity, migration) by co-culturing mammary cancer cells exhibiting different degrees of metastatic potential (MDA-MB-231>MCF-7) with fibroblasts isolated from breast healthy skin (normal fibroblasts, NFs) or from breast tumor stroma (cancer-associated fibroblasts, CAFs) in 2D or 3D (nodules) cultures. Confocal immunofluorescence analysis of the epithelial adhesion molecule E-cadherin on frozen nodule sections demonstrated that NFs and CAFs, respectively, induced or inhibited its expression in MCF-7 cells. An increase in the mesenchymal adhesion protein N-cadherin was observed in CAFs, but not in NFs, as a result of the interaction with both kinds of cancer cells. CAFs, in turn, promoted N-cadherin up-regulation in MDA-MB-231 cells and its de novo expression in MCF-7 cells. Beyond promotion of "cadherin switching", another sign of the CAF-triggered epithelial-mesenchymal transition (EMT) was the induction of vimentin expression in MCF-7 cells. Plasma membrane labeling of monolayer cultures with the fluorescent probe Laurdan showed an enhancement of the membrane fluidity in cancer cells co-cultured with NFs or CAFs. An increase in lipid packing density of fibroblast membranes was promoted by MCF-7 cells. Time-lapsed cell tracking analysis of mammary cancer cells co-cultured with NFs or CAFs revealed an enhancement of tumor cell migration velocity, even with a marked increase in the directness induced by CAFs.Our results demonstrate a reciprocal influence of mammary cancer and fibroblasts on various adhesiveness/invasiveness features. Notably, CAFs' ability to promote EMT, reduction of cell adhesion, increase in membrane fluidity, and migration velocity and directness in mammary cancer cells can be viewed as an overall progression- and invasion-promoting effect.Cristiana AngelucciGiuseppe MaulucciGina LamaGabriella ProiettiAnna ColabianchiMassimiliano PapiAlessandro MaioranaMarco De SpiritoAlessandra MiceraOmar Bijorn BalzaminoAlba Di LeoneRiccardo MasettiGigliola SicaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e50804 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cristiana Angelucci
Giuseppe Maulucci
Gina Lama
Gabriella Proietti
Anna Colabianchi
Massimiliano Papi
Alessandro Maiorana
Marco De Spirito
Alessandra Micera
Omar Bijorn Balzamino
Alba Di Leone
Riccardo Masetti
Gigliola Sica
Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.
description Interactions occurring between malignant cells and the stromal microenvironment heavily influence tumor progression. We investigated whether this cross-talk affects some molecular and functional aspects specifically correlated with the invasive phenotype of breast tumor cells (i.e. adhesion molecule expression, membrane fluidity, migration) by co-culturing mammary cancer cells exhibiting different degrees of metastatic potential (MDA-MB-231>MCF-7) with fibroblasts isolated from breast healthy skin (normal fibroblasts, NFs) or from breast tumor stroma (cancer-associated fibroblasts, CAFs) in 2D or 3D (nodules) cultures. Confocal immunofluorescence analysis of the epithelial adhesion molecule E-cadherin on frozen nodule sections demonstrated that NFs and CAFs, respectively, induced or inhibited its expression in MCF-7 cells. An increase in the mesenchymal adhesion protein N-cadherin was observed in CAFs, but not in NFs, as a result of the interaction with both kinds of cancer cells. CAFs, in turn, promoted N-cadherin up-regulation in MDA-MB-231 cells and its de novo expression in MCF-7 cells. Beyond promotion of "cadherin switching", another sign of the CAF-triggered epithelial-mesenchymal transition (EMT) was the induction of vimentin expression in MCF-7 cells. Plasma membrane labeling of monolayer cultures with the fluorescent probe Laurdan showed an enhancement of the membrane fluidity in cancer cells co-cultured with NFs or CAFs. An increase in lipid packing density of fibroblast membranes was promoted by MCF-7 cells. Time-lapsed cell tracking analysis of mammary cancer cells co-cultured with NFs or CAFs revealed an enhancement of tumor cell migration velocity, even with a marked increase in the directness induced by CAFs.Our results demonstrate a reciprocal influence of mammary cancer and fibroblasts on various adhesiveness/invasiveness features. Notably, CAFs' ability to promote EMT, reduction of cell adhesion, increase in membrane fluidity, and migration velocity and directness in mammary cancer cells can be viewed as an overall progression- and invasion-promoting effect.
format article
author Cristiana Angelucci
Giuseppe Maulucci
Gina Lama
Gabriella Proietti
Anna Colabianchi
Massimiliano Papi
Alessandro Maiorana
Marco De Spirito
Alessandra Micera
Omar Bijorn Balzamino
Alba Di Leone
Riccardo Masetti
Gigliola Sica
author_facet Cristiana Angelucci
Giuseppe Maulucci
Gina Lama
Gabriella Proietti
Anna Colabianchi
Massimiliano Papi
Alessandro Maiorana
Marco De Spirito
Alessandra Micera
Omar Bijorn Balzamino
Alba Di Leone
Riccardo Masetti
Gigliola Sica
author_sort Cristiana Angelucci
title Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.
title_short Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.
title_full Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.
title_fullStr Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.
title_full_unstemmed Epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.
title_sort epithelial-stromal interactions in human breast cancer: effects on adhesion, plasma membrane fluidity and migration speed and directness.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/5ddb606713a646948b689df132d00485
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