NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines

Leticia Huergo-Zapico, Monica Parodi, Claudia Cantoni, Chiara Lavarello, Juan L. Fernández-Martinez, Andrea Petretto, Enrique J. DeAndrés-Galiana, Mirna Balsamo, Alejandro López-Soto, Gabriella Pietra, Mattia Bugatti, Enrico Munari, Marcella Marconi, Maria Cristina Mingari, William Vermi, Lorenzo Moretta, Segundo González, Massimo Vitale

Research output: Contribution to journalArticle

Abstract

Tumor cell plasticity is a major obstacle for the cure of malignancies as it makes tumor cells highly adaptable to microenvironmental changes, enables their phenotype switching among different forms, and favors the generation of prometastatic tumor cell subsets. Phenotype switching toward more aggressive forms involves different functional, phenotypic, and morphologic changes, which are often related to the process known as epithelialtextendashmesenchymal transition (EMT). In this study, we report natural killer (NK) cells may increase the malignancy of melanoma cells by inducing changes relevant to EMT and, more broadly, to phenotype switching from proliferative to invasive forms. In coculture, NK cells induced effects on tumor cells similar to those induced by EMT-promoting cytokines, including upregulation of stemness and EMT markers, morphologic transition, inhibition of proliferation, and increased capacity for Matrigel invasion. Most changes were dependent on the engagement of NKp30 or NKG2D and the release of cytokines including IFNγ and TNFα. Moreover, EMT induction also favored escape from NK-cell attack. Melanoma cells undergoing EMT either increased NK-protective HLA-I expression on their surface or downregulated several tumor-recognizing activating receptors on NK cells. Mass spectrometrytextendashbased proteomic analysis revealed in two different melanoma cell lines a partial overlap between proteomic profiles induced by NK cells or by EMT cytokines, indicating that various processes or pathways related to tumor progression are induced by exposure to NK cells.Significance: NK cells can induce prometastatic properties on melanoma cells that escape from killing, providing important clues to improve the efficacy of NK cells in innovative antitumor therapies. Cancer Res; 78(14); 3913textendash25. textcopyright2018 AACR.
Original languageUndefined/Unknown
Pages (from-to)3913-3925
Number of pages13
JournalCancer Research
Volume78
Issue number14
DOIs
Publication statusPublished - 2018

Cite this

NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines. / Huergo-Zapico, Leticia; Parodi, Monica; Cantoni, Claudia; Lavarello, Chiara; Fernández-Martinez, Juan L.; Petretto, Andrea; DeAndrés-Galiana, Enrique J.; Balsamo, Mirna; López-Soto, Alejandro; Pietra, Gabriella; Bugatti, Mattia; Munari, Enrico; Marconi, Marcella; Mingari, Maria Cristina; Vermi, William; Moretta, Lorenzo; González, Segundo; Vitale, Massimo.

In: Cancer Research, Vol. 78, No. 14, 2018, p. 3913-3925.

Research output: Contribution to journalArticle

Huergo-Zapico, L, Parodi, M, Cantoni, C, Lavarello, C, Fernández-Martinez, JL, Petretto, A, DeAndrés-Galiana, EJ, Balsamo, M, López-Soto, A, Pietra, G, Bugatti, M, Munari, E, Marconi, M, Mingari, MC, Vermi, W, Moretta, L, González, S & Vitale, M 2018, 'NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines', Cancer Research, vol. 78, no. 14, pp. 3913-3925. https://doi.org/10.1158/0008-5472.CAN-17-1891
Huergo-Zapico, Leticia ; Parodi, Monica ; Cantoni, Claudia ; Lavarello, Chiara ; Fernández-Martinez, Juan L. ; Petretto, Andrea ; DeAndrés-Galiana, Enrique J. ; Balsamo, Mirna ; López-Soto, Alejandro ; Pietra, Gabriella ; Bugatti, Mattia ; Munari, Enrico ; Marconi, Marcella ; Mingari, Maria Cristina ; Vermi, William ; Moretta, Lorenzo ; González, Segundo ; Vitale, Massimo. / NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines. In: Cancer Research. 2018 ; Vol. 78, No. 14. pp. 3913-3925.
@article{73559b8705a94a26bf5d68cb7c087684,
title = "NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines",
abstract = "Tumor cell plasticity is a major obstacle for the cure of malignancies as it makes tumor cells highly adaptable to microenvironmental changes, enables their phenotype switching among different forms, and favors the generation of prometastatic tumor cell subsets. Phenotype switching toward more aggressive forms involves different functional, phenotypic, and morphologic changes, which are often related to the process known as epithelialtextendashmesenchymal transition (EMT). In this study, we report natural killer (NK) cells may increase the malignancy of melanoma cells by inducing changes relevant to EMT and, more broadly, to phenotype switching from proliferative to invasive forms. In coculture, NK cells induced effects on tumor cells similar to those induced by EMT-promoting cytokines, including upregulation of stemness and EMT markers, morphologic transition, inhibition of proliferation, and increased capacity for Matrigel invasion. Most changes were dependent on the engagement of NKp30 or NKG2D and the release of cytokines including IFNγ and TNFα. Moreover, EMT induction also favored escape from NK-cell attack. Melanoma cells undergoing EMT either increased NK-protective HLA-I expression on their surface or downregulated several tumor-recognizing activating receptors on NK cells. Mass spectrometrytextendashbased proteomic analysis revealed in two different melanoma cell lines a partial overlap between proteomic profiles induced by NK cells or by EMT cytokines, indicating that various processes or pathways related to tumor progression are induced by exposure to NK cells.Significance: NK cells can induce prometastatic properties on melanoma cells that escape from killing, providing important clues to improve the efficacy of NK cells in innovative antitumor therapies. Cancer Res; 78(14); 3913textendash25. textcopyright2018 AACR.",
author = "Leticia Huergo-Zapico and Monica Parodi and Claudia Cantoni and Chiara Lavarello and Fern{\'a}ndez-Martinez, {Juan L.} and Andrea Petretto and DeAndr{\'e}s-Galiana, {Enrique J.} and Mirna Balsamo and Alejandro L{\'o}pez-Soto and Gabriella Pietra and Mattia Bugatti and Enrico Munari and Marcella Marconi and Mingari, {Maria Cristina} and William Vermi and Lorenzo Moretta and Segundo Gonz{\'a}lez and Massimo Vitale",
year = "2018",
doi = "10.1158/0008-5472.CAN-17-1891",
language = "Non definita",
volume = "78",
pages = "3913--3925",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "14",

}

TY - JOUR

T1 - NK-cell Editing Mediates Epithelial-to-Mesenchymal Transition via Phenotypic and Proteomic Changes in Melanoma Cell Lines

AU - Huergo-Zapico, Leticia

AU - Parodi, Monica

AU - Cantoni, Claudia

AU - Lavarello, Chiara

AU - Fernández-Martinez, Juan L.

AU - Petretto, Andrea

AU - DeAndrés-Galiana, Enrique J.

AU - Balsamo, Mirna

AU - López-Soto, Alejandro

AU - Pietra, Gabriella

AU - Bugatti, Mattia

AU - Munari, Enrico

AU - Marconi, Marcella

AU - Mingari, Maria Cristina

AU - Vermi, William

AU - Moretta, Lorenzo

AU - González, Segundo

AU - Vitale, Massimo

PY - 2018

Y1 - 2018

N2 - Tumor cell plasticity is a major obstacle for the cure of malignancies as it makes tumor cells highly adaptable to microenvironmental changes, enables their phenotype switching among different forms, and favors the generation of prometastatic tumor cell subsets. Phenotype switching toward more aggressive forms involves different functional, phenotypic, and morphologic changes, which are often related to the process known as epithelialtextendashmesenchymal transition (EMT). In this study, we report natural killer (NK) cells may increase the malignancy of melanoma cells by inducing changes relevant to EMT and, more broadly, to phenotype switching from proliferative to invasive forms. In coculture, NK cells induced effects on tumor cells similar to those induced by EMT-promoting cytokines, including upregulation of stemness and EMT markers, morphologic transition, inhibition of proliferation, and increased capacity for Matrigel invasion. Most changes were dependent on the engagement of NKp30 or NKG2D and the release of cytokines including IFNγ and TNFα. Moreover, EMT induction also favored escape from NK-cell attack. Melanoma cells undergoing EMT either increased NK-protective HLA-I expression on their surface or downregulated several tumor-recognizing activating receptors on NK cells. Mass spectrometrytextendashbased proteomic analysis revealed in two different melanoma cell lines a partial overlap between proteomic profiles induced by NK cells or by EMT cytokines, indicating that various processes or pathways related to tumor progression are induced by exposure to NK cells.Significance: NK cells can induce prometastatic properties on melanoma cells that escape from killing, providing important clues to improve the efficacy of NK cells in innovative antitumor therapies. Cancer Res; 78(14); 3913textendash25. textcopyright2018 AACR.

AB - Tumor cell plasticity is a major obstacle for the cure of malignancies as it makes tumor cells highly adaptable to microenvironmental changes, enables their phenotype switching among different forms, and favors the generation of prometastatic tumor cell subsets. Phenotype switching toward more aggressive forms involves different functional, phenotypic, and morphologic changes, which are often related to the process known as epithelialtextendashmesenchymal transition (EMT). In this study, we report natural killer (NK) cells may increase the malignancy of melanoma cells by inducing changes relevant to EMT and, more broadly, to phenotype switching from proliferative to invasive forms. In coculture, NK cells induced effects on tumor cells similar to those induced by EMT-promoting cytokines, including upregulation of stemness and EMT markers, morphologic transition, inhibition of proliferation, and increased capacity for Matrigel invasion. Most changes were dependent on the engagement of NKp30 or NKG2D and the release of cytokines including IFNγ and TNFα. Moreover, EMT induction also favored escape from NK-cell attack. Melanoma cells undergoing EMT either increased NK-protective HLA-I expression on their surface or downregulated several tumor-recognizing activating receptors on NK cells. Mass spectrometrytextendashbased proteomic analysis revealed in two different melanoma cell lines a partial overlap between proteomic profiles induced by NK cells or by EMT cytokines, indicating that various processes or pathways related to tumor progression are induced by exposure to NK cells.Significance: NK cells can induce prometastatic properties on melanoma cells that escape from killing, providing important clues to improve the efficacy of NK cells in innovative antitumor therapies. Cancer Res; 78(14); 3913textendash25. textcopyright2018 AACR.

U2 - 10.1158/0008-5472.CAN-17-1891

DO - 10.1158/0008-5472.CAN-17-1891

M3 - Articolo

VL - 78

SP - 3913

EP - 3925

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 14

ER -