How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease
Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we d...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-03-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/22/5/2550 |
id |
doaj-fcfc9c7608f64495823a4e7f2a7712b0 |
---|---|
record_format |
Article |
spelling |
doaj-fcfc9c7608f64495823a4e7f2a7712b02021-03-05T00:00:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01222550255010.3390/ijms22052550How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer DiseaseRoberto Zefferino0Claudia Piccoli1Sante Di Gioia2Nazzareno Capitanio3Massimo Conese4Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, ItalyDepartment of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, ItalyDepartment of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, ItalyConnexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: “Activating Invasion and Metastasis” and the “Avoiding Immune Destruction”, with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner.https://www.mdpi.com/1422-0067/22/5/2550connexinpannexinhemichannelsgap junction intercellular communicationtumor microenvironmentepithelial-mesenchymal transition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Roberto Zefferino Claudia Piccoli Sante Di Gioia Nazzareno Capitanio Massimo Conese |
spellingShingle |
Roberto Zefferino Claudia Piccoli Sante Di Gioia Nazzareno Capitanio Massimo Conese How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease International Journal of Molecular Sciences connexin pannexin hemichannels gap junction intercellular communication tumor microenvironment epithelial-mesenchymal transition |
author_facet |
Roberto Zefferino Claudia Piccoli Sante Di Gioia Nazzareno Capitanio Massimo Conese |
author_sort |
Roberto Zefferino |
title |
How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease |
title_short |
How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease |
title_full |
How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease |
title_fullStr |
How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease |
title_full_unstemmed |
How Cells Communicate with Each Other in the Tumor Microenvironment: Suggestions to Design Novel Therapeutic Strategies in Cancer Disease |
title_sort |
how cells communicate with each other in the tumor microenvironment: suggestions to design novel therapeutic strategies in cancer disease |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
Connexin- and pannexin (Panx)-formed hemichannels (HCs) and gap junctions (GJs) operate an interaction with the extracellular matrix and GJ intercellular communication (GJIC), and on account of this they are involved in cancer onset and progression towards invasiveness and metastatization. When we deal with cancer, it is not correct to omit the immune system, as well as neglecting its role in resisting or succumbing to formation and progression of incipient neoplasia until the formation of micrometastasis, nevertheless what really occurs in the tumor microenvironment (TME), which are the main players and which are the tumor or body allies, is still unclear. The goal of this article is to discuss how the pivotal players act, which can enhance or contrast cancer progression during two important process: “Activating Invasion and Metastasis” and the “Avoiding Immune Destruction”, with a particular emphasis on the interplay among GJIC, Panx-HCs, and the purinergic system in the TME without disregarding the inflammasome and cytokines thereof derived. In particular, the complex and contrasting roles of Panx1/P2X7R signalosome in tumor facilitation and/or inhibition is discussed in regard to the early/late phases of the carcinogenesis. Finally, considering this complex interplay in the TME between cancer cells, stromal cells, immune cells, and focusing on their means of communication, we should be capable of revealing harmful messages that help the cancer growth and transform them in body allies, thus designing novel therapeutic strategies to fight cancer in a personalized manner. |
topic |
connexin pannexin hemichannels gap junction intercellular communication tumor microenvironment epithelial-mesenchymal transition |
url |
https://www.mdpi.com/1422-0067/22/5/2550 |
work_keys_str_mv |
AT robertozefferino howcellscommunicatewitheachotherinthetumormicroenvironmentsuggestionstodesignnoveltherapeuticstrategiesincancerdisease AT claudiapiccoli howcellscommunicatewitheachotherinthetumormicroenvironmentsuggestionstodesignnoveltherapeuticstrategiesincancerdisease AT santedigioia howcellscommunicatewitheachotherinthetumormicroenvironmentsuggestionstodesignnoveltherapeuticstrategiesincancerdisease AT nazzarenocapitanio howcellscommunicatewitheachotherinthetumormicroenvironmentsuggestionstodesignnoveltherapeuticstrategiesincancerdisease AT massimoconese howcellscommunicatewitheachotherinthetumormicroenvironmentsuggestionstodesignnoveltherapeuticstrategiesincancerdisease |
_version_ |
1724231539578896384 |