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Cancers
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Extracellular Matrix in the Tumor Microenvironment—Role in Immune Modulation and...
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Extracellular Matrix in the Tumor Microenvironment—Role in Immune Modulation and Impact on Cancer Therapy

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 9155

Special Issue Editors

Dr. Luca Urbani

E-Mail Website
Guest Editor
Head of Liver Regeneration & Tissue Engineering Group, Institute of Hepatology, Foundation for Liver Research, London SE5 9NT, UK
Interests: Immunological Properties of the Extracellular Matrix, Extracellular Matrix-Derived Scaffolds in Angiogenesis, Tissue Regeneration, Transplantation, 3D Cell Culture, Stem Cell Differentiation, Disease Modelling and Immune-Modulation.
Dr. Martina Piccoli

E-Mail Website
Co-Guest Editor
Laboratory of Tissue Engineering, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, 35127 Padova, Italy
Interests: skeletal muscle; decellularized tissues; extracellular matrix; 3D culture models; 3D bioprinting
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The extracellular matrix (ECM) is a three-dimensional scaffold made up of intricate networks of connective tissue, maintaining organ shape and structure. It is now being recognized also as a vital and versatile contributor to organ maintenance and pathological states as changes in ECM protein composition can significantly alter structure and function of an organ. In the tumour microenvironment, the ECM influences tumor development and progression, including metastasis formation. ECM dysregulation promotes cancer cell invasion, induces angiogenesis and facilitates immune cell infiltration via specific interactions between ECM proteins and cancer and cancer-associated cells. Activated immune cells closely interact with ECM, which may affect the outcome of tumor progression. The biomechanical characteristics of the ECM, such as stiffness and tension, also shape the microenvironment of tumors.

Due to the impact that the ECM has on cancer environment and progression, the necessity of ECM components to be included in disease modelling continues to increase. Mapping ECM-cell interactions and ECM composition is highly important to understand cancer response to chemotherapy and potentially give rise to alternative targets for therapy.

The purpose of this Special Issue is to emphasize the influence of the ECM on the tumor microenvironment promoting cancer progression and impacting response to chemotherapeutic drugs. The issue aims to collect current bodies of work underlining ECM|

Dr. Luca Urbani
Dr. Martina Piccoli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Extracellular matrix
  • Tumor microenvironment
  • Cancer immune modulation
  • 3D Cancer Models
  • Cancer therapy
  • Cancer angiogenesis

Published Papers (3 papers)

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Research

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21 pages, 4299 KiB  
Article
Comprehensive Analysis Identifies Ameloblastin-Related Competitive Endogenous RNA as a Prognostic Biomarker for Testicular Germ Cell Tumour
by Tianxiang Geng, Catherine Anne Heyward, Xi Chen, Mengxue Zheng, Yang Yang and Janne Elin Reseland
Cancers 2022, 14(8), 1870; https://doi.org/10.3390/cancers14081870 - 07 Apr 2022
Cited by 4 | Viewed by 2275
Abstract
Testicular Germ Cell Tumour (TGCT) is one of the most common tumours in young men. Increasing evidence shows that the extracellular matrix has a key role in the prognosis and metastasis of various human cancers. This study analysed the relationship between the matrix [...] Read more.
Testicular Germ Cell Tumour (TGCT) is one of the most common tumours in young men. Increasing evidence shows that the extracellular matrix has a key role in the prognosis and metastasis of various human cancers. This study analysed the relationship between the matrix protein ameloblastin (AMBN) and potential biological markers associated with TGCT diagnosis and prognosis. The relationship between AMBN and TGCT prognosis was determined by bioinformatic analysis using the expression profiles of three RNAs (long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs) from The Cancer Genome Atlas (TCGA) database, and available clinical information of the corresponding patients. Prediction and validation of competitive endogenous RNA (ceRNA) regulatory networks related to AMBN was performed. AMBN and its associated ceRNA regulatory network were found to be related to the recurrence of TGCT, and LINC02701 may be used as a diagnostic factor in TGCT. Furthermore, we identified PELATON (Plaque Enriched LncRNA In Atherosclerotic And Inflammatory Bowel Macrophage Regulation) as an independent prognostic factor for TGCT progression-free interval. Full article
(This article belongs to the Special Issue Extracellular Matrix in the Tumor Microenvironment—Role in Immune Modulation and Impact on Cancer Therapy)
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19 pages, 2995 KiB  
Article
Tumor Cells and the Extracellular Matrix Dictate the Pro-Tumoral Profile of Macrophages in CRC
by Sara Coletta, Silvia Lonardi, Francesca Sensi, Edoardo D’Angelo, Matteo Fassan, Salvatore Pucciarelli, Arianna Valzelli, Andrea Biccari, William Vermi, Chiara Della Bella, Annica Barizza, Mario Milco D’Elios, Marina de Bernard, Marco Agostini and Gaia Codolo
Cancers 2021, 13(20), 5199; https://doi.org/10.3390/cancers13205199 - 16 Oct 2021
Cited by 5 | Viewed by 2647
Abstract
Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. In colorectal cancer (CRC), a strong infiltration of TAMs is accompanied by a decrease in effector T cells and an increase in the metastatic potential of CRC. We investigated the functional profile of [...] Read more.
Tumor-associated macrophages (TAMs) are major components of the tumor microenvironment. In colorectal cancer (CRC), a strong infiltration of TAMs is accompanied by a decrease in effector T cells and an increase in the metastatic potential of CRC. We investigated the functional profile of TAMs infiltrating CRC tissue by immunohistochemistry, flow cytometry, ELISA, and qRT-PCR and their involvement in impairing the activation of effector T cells. In CRC biopsies, we evidenced a high percentage of macrophages with low expression of the antigen-presenting complex MHC-II and high expression of CD206. Monocytes co-cultured with tumor cells or a decellularized tumor matrix differentiated toward a pro-tumoral macrophage phenotype characterized by decreased expression of MHC-II and CD86 and increased expression of CD206 and an abundant release of pro-tumoral cytokines and chemokines. We demonstrated that the hampered expression of MHC-II in macrophages is due to the downregulation of the MHC-II transactivator CIITA and that this effect relies on increased expression of miRNAs targeting CIITA. As a result, macrophages become unable to present antigens to CD4 T lymphocytes. Our data suggest that the tumor microenvironment contributes to defining a pro-tumoral profile of macrophages infiltrating CRC tissue with impaired capacity to activate T cell effector functions. Full article
(This article belongs to the Special Issue Extracellular Matrix in the Tumor Microenvironment—Role in Immune Modulation and Impact on Cancer Therapy)
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Review

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21 pages, 1211 KiB  
Review
Interplay between Cellular and Non-Cellular Components of the Tumour Microenvironment in Hepatocellular Carcinoma
by Tamás Sükei, Elena Palma and Luca Urbani
Cancers 2021, 13(21), 5586; https://doi.org/10.3390/cancers13215586 - 08 Nov 2021
Cited by 11 | Viewed by 3314
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Currently, treatments available for advanced HCC provide dismal chances of survival, thus there is an urgent need to develop more effective therapeutic strategies. While much of the focus of recent [...] Read more.
Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Currently, treatments available for advanced HCC provide dismal chances of survival, thus there is an urgent need to develop more effective therapeutic strategies. While much of the focus of recent decades has been on targeting malignant cells, promising results have emerged from targeting the tumour microenvironment (TME). The extracellular matrix (ECM) is the main non-cellular component of the TME and it profoundly changes during tumorigenesis to promote the growth and survival of malignant cells. Despite this, many in vitro models for drug testing fail to consider the TME leading to a high failure rate in clinical trials. Here, we present an overview of the function and properties of the ECM in the liver and how these change during malignant transformation. We also discuss the relationship between immune cells and ECM in the TME in HCC. Lastly, we present advanced, 3D culture techniques of cancer modelling and argue that the incorporation of TME components into these is essential to better recapitulate the complex interactions within the TME. Full article
(This article belongs to the Special Issue Extracellular Matrix in the Tumor Microenvironment—Role in Immune Modulation and Impact on Cancer Therapy)
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