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Extracellular Matrix and Cancer: An Intricate Affair

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 10963

Special Issue Editor

IRCCS Centro Di Riferimento Oncologico Aviano, 33081 Aviano, Italy
Interests: ECM; tumor microenvironment; angiogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The extracellular matrix (ECM) is composed of glycoproteins, proteoglycans and glycosaminoglycans displaying distinct physical, biochemical, and biomechanical properties. The ECM is the home where cells live and plays a vital role in maintaining tissue homeostasis.

However, the ECM is not only a mere scaffold for the cells, but also, it actively affects cell behavior, impacting on their viability, differentiation, proliferation and migration, as well as functioning as a reservoir of growth factors that modulate their activity and affinity with the cognate receptors.

For these reasons, the ECM’s composition is tightly regulated under normal conditions and extensively remodeled in pathological conditions such as cancer. Abnormal ECM composition impacts on cancer progression either directly, by promoting cellular transformation and metastasis, or indirectly, impinging on microenvironmental cues such as the inflammatory response and angiogenesis.

For this Special Issue, I encourage the submission of original research articles or reviews that highlight the importance of ECM in cancer onset and progression.

Dr. Maurizio Mongiat
Guest Editor

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.

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Keywords

  • extracellular matrix
  • tumor microenvironment
  • angiogenesis
  • inflammation
  • cancer

Published Papers (6 papers)

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Editorial

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3 pages, 180 KiB  
Editorial
Extracellular Matrix and Cancer: An Intricate Affair
by Maurizio Mongiat
Int. J. Mol. Sci. 2023, 24(18), 13969; https://doi.org/10.3390/ijms241813969 - 12 Sep 2023
Viewed by 572
Abstract
In complex multicellular eukaryotes, the extracellular matrix (ECM) is an essential component of the organism, not only providing structure to the tissues, but also granting cellular cooperation through the engagement of an intricate crosstalk between all cell types [...] Full article
(This article belongs to the Special Issue Extracellular Matrix and Cancer: An Intricate Affair)

Research

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12 pages, 1998 KiB  
Article
Dermatopontin Influences the Development of Obesity-Associated Colon Cancer by Changes in the Expression of Extracellular Matrix Proteins
by Victoria Catalán, Paula Domench, Javier Gómez-Ambrosi, Beatriz Ramírez, Sara Becerril, Amaia Mentxaka, Amaia Rodríguez, Víctor Valentí, Rafael Moncada, Jorge Baixauli, Camilo Silva, Javier Escalada and Gema Frühbeck
Int. J. Mol. Sci. 2022, 23(16), 9222; https://doi.org/10.3390/ijms23169222 - 17 Aug 2022
Cited by 5 | Viewed by 1873
Abstract
Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to [...] Read more.
Dysfunctional adipose tissue (AT) in the context of obesity leads to chronic inflammation together with an altered extracellular matrix (ECM) remodelling, favouring cancer development and progression. Recently, the influence of dermatopontin (DPT) in AT remodelling and inflammation has been proposed. We aimed to evaluate the role of DPT in the development of obesity-associated colon cancer (CC). Samples obtained from 73 subjects [26 lean (LN) and 47 with obesity (OB)] were used in a case-control study. Enrolled subjects were further subclassified according to the established diagnostic protocol for CC (42 without CC and 31 with CC). In vitro studies in the adenocarcinoma HT-29 cell line were performed to analyse the impact of pro- and anti-inflammatory mediators on the transcript levels of DPT as well as the effect of DPT on ECM remodelling and inflammation. Although obesity increased (p < 0.05) the circulating levels of DPT, its concentrations were significantly decreased (p < 0.05) in patients with CC. Gene expression levels of DPT in the colon from patients with CC were downregulated and, oppositely, a tendency towards increased mRNA levels in visceral AT was found. We further showed that DPT expression levels in HT-29 cells were enhanced (p < 0.05) by inflammatory factors (LPS, TNF-α and TGF-β), whereas the anti-inflammatory IL-4 decreased (p < 0.05) its expression levels. We also demonstrated that DPT upregulated (p < 0.05) the mRNA of key molecules involved in ECM remodelling (COL1A1, COL5A3, TNC and VEGFA) whereas decorin (DCN) expression was downregulated (p < 0.05) in HT-29 cells. Finally, we revealed that the adipocyte-conditioned medium obtained from volunteers with OB enhanced (p < 0.01) the expression of DPT in HT-29 and Caco-2 cells. The decreased circulating and expression levels of DPT in the colon together with the tendency towards increased levels in visceral AT in patients with CC and its influence on the expression of ECM proteins suggest a possible role of DPT in the OB-associated CC. Full article
(This article belongs to the Special Issue Extracellular Matrix and Cancer: An Intricate Affair)
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18 pages, 3338 KiB  
Article
Unusual Association of NF-κB Components in Tumor-Associated Macrophages (TAMs) Promotes HSPG2-Mediated Immune-Escaping Mechanism in Breast Cancer
by Veronica De Paolis, Fabio Maiullari, Maila Chirivì, Marika Milan, Chiara Cordiglieri, Francesca Pagano, Alessandra Rita La Manna, Elena De Falco, Claudia Bearzi, Roberto Rizzi and Chiara Parisi
Int. J. Mol. Sci. 2022, 23(14), 7902; https://doi.org/10.3390/ijms23147902 - 18 Jul 2022
Cited by 5 | Viewed by 1982
Abstract
The cellular heterogeneity of the tumor environment of breast cancer (BC) is extremely complex and includes different actors such as neoplastic, stromal, and immunosuppressive cells, which contribute to the chemical and mechanical modification of the environment surrounding the tumor-exasperating immune-escaping mechanisms. In addition [...] Read more.
The cellular heterogeneity of the tumor environment of breast cancer (BC) is extremely complex and includes different actors such as neoplastic, stromal, and immunosuppressive cells, which contribute to the chemical and mechanical modification of the environment surrounding the tumor-exasperating immune-escaping mechanisms. In addition to molecular signals that make the tumor microenvironment (TME) unacceptable for the penetrance of the immune system, the physical properties of tumoral extracellular matrix (tECM) also have carved out a fundamental role in the processes of the protection of the tumor niche. Tumor-associated macrophages (TAMs), with an M2 immunosuppressive phenotype, are important determinants for the establishment of a tumor phenotype excluded from T cells. NF-κB transcription factors orchestrate innate immunity and represent the common thread between inflammation and cancer. Many studies have focused on canonical activation of NF-κB; however, activation of non-canonical signaling predicts poor survival and resistance to therapy. In this scenario, we demonstrated the existence of an unusual association of NF-κB components in TAMs that determines the deposition of HSPG2 that affects the stiffness of tECM. These results highlight a new mechanism counterbalanced between physical factors and a new perspective of mechano-pathology to be targeted to counteract immune evasion in BC. Full article
(This article belongs to the Special Issue Extracellular Matrix and Cancer: An Intricate Affair)
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Review

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16 pages, 1886 KiB  
Review
Antitumor Properties of Matrikines of Different Origins: Prospects and Problems of Their Application
by Aleksandr Popov, Emma Kozlovskaya, Tatyana Rutckova, Olga Styshova, Aleksey Vakhrushev, Elena Kupera and Ludmila Tekutyeva
Int. J. Mol. Sci. 2023, 24(11), 9502; https://doi.org/10.3390/ijms24119502 - 30 May 2023
Cited by 3 | Viewed by 1072
Abstract
Matrikines (MKs) can be a rich source of functional nutrition components and additional therapy, thereby contributing to human health care and reducing the risk of developing serious diseases, including cancer. Currently, functionally active MKs as products of enzymatic transformation by matrix metalloproteinases (MMPs) [...] Read more.
Matrikines (MKs) can be a rich source of functional nutrition components and additional therapy, thereby contributing to human health care and reducing the risk of developing serious diseases, including cancer. Currently, functionally active MKs as products of enzymatic transformation by matrix metalloproteinases (MMPs) are used for various biomedical purposes. Due to the absence of toxic side effects, low species specificity, relatively small size, and presence of various targets at the cell membranes, MKs often exhibit antitumor properties and, therefore, are promising agents for antitumor combination therapy. This review summarizes and analyzes the current data on the antitumor activity of MKs of different origins, discusses the problems and prospects for their therapeutic use, and evaluates the experimental results of studying the antitumor properties of MKs from different echinoderm species generated with the help of a complex of proteolytic enzymes from red king crab Paralithodes camtschatica. Special attention is paid to the analysis of possible mechanisms of the antitumor action of various functionally active MKs, products of the enzymatic activity of various MMPs, and the existing problems for their use in antitumor therapy. Full article
(This article belongs to the Special Issue Extracellular Matrix and Cancer: An Intricate Affair)
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21 pages, 587 KiB  
Review
Glucocorticoid Effects on Proteoglycans and Glycosaminoglycans
by Anastasia V. Strokotova and Elvira V. Grigorieva
Int. J. Mol. Sci. 2022, 23(24), 15678; https://doi.org/10.3390/ijms232415678 - 10 Dec 2022
Cited by 3 | Viewed by 1368
Abstract
Glucocorticoids are steroid hormones that play diverse roles in numerous normal and pathological processes. They are actively used to treat a wide variety of diseases, including neurodegenerative and inflammatory diseases, cancers, and COVID-19, among others. However, the long-term use of glucocorticoids is associated [...] Read more.
Glucocorticoids are steroid hormones that play diverse roles in numerous normal and pathological processes. They are actively used to treat a wide variety of diseases, including neurodegenerative and inflammatory diseases, cancers, and COVID-19, among others. However, the long-term use of glucocorticoids is associated with numerous side effects. Molecular mechanisms of these negative side effects are not completely understood. Recently, arguments have been made that one such mechanisms may be related to the influence of glucocorticoids on O-glycosylated components of the cell surface and extracellular matrix, in particular on proteoglycans and glycosaminoglycans. The potential toxic effects of glucocorticoids on these glycosylated macromolecules are particularly meaningful for brain physiology because proteoglycans/glycosaminoglycans are the main extracellular components of brain tissue. Here, we aim to review the known effects of glucocorticoids on proteoglycan expression and glycosaminoglycan content in different tissues, with a specific focus on the brain. Full article
(This article belongs to the Special Issue Extracellular Matrix and Cancer: An Intricate Affair)
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28 pages, 1977 KiB  
Review
Collagen Remodeling along Cancer Progression Providing a Novel Opportunity for Cancer Diagnosis and Treatment
by Kena Song, Zhangqing Yu, Xiangyang Zu, Guoqiang Li, Zhigang Hu and Yun Xue
Int. J. Mol. Sci. 2022, 23(18), 10509; https://doi.org/10.3390/ijms231810509 - 10 Sep 2022
Cited by 16 | Viewed by 3402
Abstract
The extracellular matrix (ECM) is a significant factor in cancer progression. Collagens, as the main component of the ECM, are greatly remodeled alongside cancer development. More and more studies have confirmed that collagens changed from a barrier to providing assistance in cancer development. [...] Read more.
The extracellular matrix (ECM) is a significant factor in cancer progression. Collagens, as the main component of the ECM, are greatly remodeled alongside cancer development. More and more studies have confirmed that collagens changed from a barrier to providing assistance in cancer development. In this course, collagens cause remodeling alongside cancer progression, which in turn, promotes cancer development. The interaction between collagens and tumor cells is complex with biochemical and mechanical signals intervention through activating diverse signal pathways. As the mechanism gradually clears, it becomes a new target to find opportunities to diagnose and treat cancer. In this review, we investigated the process of collagen remodeling in cancer progression and discussed the interaction between collagens and cancer cells. Several typical effects associated with collagens were highlighted in the review, such as fibrillation in precancerous lesions, enhancing ECM stiffness, promoting angiogenesis, and guiding invasion. Then, the values of cancer diagnosis and prognosis were focused on. It is worth noting that several generated fragments in serum were reported to be able to be biomarkers for cancer diagnosis and prognosis, which is beneficial for clinic detection. At a glance, a variety of reported biomarkers were summarized. Many collagen-associated targets and drugs have been reported for cancer treatment in recent years. The new targets and related drugs were discussed in the review. The mass data were collected and classified by mechanism. Overall, the interaction of collagens and tumor cells is complicated, in which the mechanisms are not completely clear. A lot of collagen-associated biomarkers are excavated for cancer diagnosis. However, new therapeutic targets and related drugs are almost in clinical trials, with merely a few in clinical applications. So, more efforts are needed in collagens-associated studies and drug development for cancer research and treatment. Full article
(This article belongs to the Special Issue Extracellular Matrix and Cancer: An Intricate Affair)
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