Mediators of extracellular matrix degradation and inflammation: A new team of possible biomarkers for oral squamous cell carcinoma stage

Rădulescu, Radu; Totan, Alexandra; Imre, Marina; Miricescu, Daniela; Didilescu, Andreea Cristiana; Greabu, Maria

doi:10.3892/etm.2021.10309

Cited by 8 publications

(6 citation statements)

References 49 publications

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“…The immune-inflammatory system and matrix metalloproteases were previously demonstrated to be overrepresented in PeCa compared to normal penile tissues ( 10 , 43 ). In oral carcinomas, high levels of pro-inflammatory cytokines affect the TME by increasing ECM degradation via MMPs during disease progression ( 44 ). Our findings suggest that interactions between inflammation and matrix remodeling have a crucial role in penile carcinogenesis and progression.…”

Section: Discussionmentioning

confidence: 99%

Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer

Cury

Kuasne²,

Souza³

et al. 2022

Front. Oncol.

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Extracellular matrix (ECM) remodeling and inflammation have been reported in penile carcinomas (PeCa). However, the cell types and cellular crosstalk involved in PeCa are unexplored. We aimed to characterize the complexity of cells and pathways involved in the tumor microenvironment (TME) in PeCa and propose target molecules associated with the TME. We first investigated the prognostic impact of cell types with a secretory profile to identify drug targets that modulate TME-enriched cells. The secretome analysis using the PeCa transcriptome revealed the enrichment of inflammation and extracellular matrix pathways. Twenty-three secreted factors were upregulated, mainly collagens and matrix metalloproteinases (MMPs). The deregulation of collagens and MMPs was confirmed by Quantitative reverse transcription - polymerase chain reaction (RT-qPCR). Further, the deconvolution method (digital cytometry) of the bulk samples revealed a high proportion of macrophages and dendritic cells (DCs) and B cells. Increased DCs and B cells were associated with better survival. A high proportion of cancer-associated fibroblasts (CAFs) was observed in low-survival patients. Patients with increased CAFs had decreased immune cell proportions. The treatment with the MMP inhibitor GM6001 in CAF cells derived from PeCa resulted in altered cell viability. We reported a crosstalk between immune cells and CAFs, and the proportion of these cell populations was associated with prognosis. We demonstrate that a drug targeting MMPs modulates CAFs, expanding the therapeutic options of PeCa.

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Section: Discussionmentioning

confidence: 99%

Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer

Cury

Kuasne²,

Souza³

et al. 2022

Front. Oncol.

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“…As expected, the expression and activity of MMPs increase in OPMD and OSCC tissues in parallel with CD147 hyperactivation [ 18 , 19 ]. A trend opposite to that of MMPs is followed by their antagonists, such as the Tissue Inhibitors of MMPs (TIMPs), whose amounts in OSCC lesions are lower than those found in healthy oral mucosa [ 83 ] and inversely related to CD147 expression ( Table 2 ) [ 47 ].…”

Section: Cd147 and Invasive Oscc Developmentmentioning

confidence: 99%

“…It must be highlighted that the activation of NF-kB induced by CD147 results not only in the expression of inflammatory mediators but also in the synthesis of pro-invasive MMP-2 and MMP-9 ( Table 2 , Figure 1 ) [ 135 , 136 , 137 ]. Moreover, by triggering NF-kB-promoted MMPs expression, the concerted actions of CD147 and inflammatory cytokines cause the infiltration of OPMD or OSCC tissues by neutrophils and/or monocytes [ 26 , 28 , 83 ]. While neutrophils produce and release high levels of MMP-9 [ 8 , 83 ], monocytes differentiate into macrophages [ 26 ].…”

Section: Reciprocal Interaction Between Cd147 and Opmd/oscc-associate...mentioning

confidence: 99%

“…Moreover, by triggering NF-kB-promoted MMPs expression, the concerted actions of CD147 and inflammatory cytokines cause the infiltration of OPMD or OSCC tissues by neutrophils and/or monocytes [ 26 , 28 , 83 ]. While neutrophils produce and release high levels of MMP-9 [ 8 , 83 ], monocytes differentiate into macrophages [ 26 ]. In this context, IL-1, IL-6, and IL-8 induce the polarization of macrophages to the protumor M2 phenotype, hence accelerating OSCC progression, both in humans [ 138 ] and in animal models [ 104 ].…”

Section: Reciprocal Interaction Between Cd147 and Opmd/oscc-associate...mentioning

confidence: 99%

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The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

Barillari

Melaiu

Gargari

et al. 2022

IJMS

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Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC.

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“…Inflammation, apoptosis, and host resistance are mostly mediated by cytokines, which also act as signaling molecules in cell-cell interactions [15]. A recent study also reported that interleukin-6 (IL-6) and interleukin-8 (IL-8) are candidate markers for oral squamous cell carcinoma [16]. A growing body of research shows that increased CD44s, CD44v6, IL-1β, CXCL1, and CXCR2 expressions have been associated with different kinds of tumors [12,[17][18][19], but few studies have investigated those biomarkers in tumors of salivary glands.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of CD44s, CD44v6, CXCR2, CXCL1, and IL-1β in Benign and Malignant Tumors of Salivary Glands

et al. 2022

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Background: Several studies have reported an association between high expression of CD44 in different types of cancer. However, no study has reported a link among CD44 expression, other biomarkers, and the aggressiveness of salivary gland tumors. Methods: A total of 38 specimens were obtained from non-tumorous salivary glands, benign and malignant tumors in salivary glands. Immunohistochemical analyses of CD44s, CD44v6, IL-1β, CXCL1, and CXCR2 were performed, and the area of positive cells was assessed. Results: We found that both CD44s and CXCR2 expression were increased in the benign and malignant groups. CD44v6 was also increased in both groups, but it had the highest level in the malignant group. IL-1β was the only biomarker that increased significantly in the malignant group in comparison to the other two groups. Conclusions: CD44s, CD44v6, CXCR2, and IL-1β expressions were found to be higher in salivary gland tumors. However, IL-1β alone may play a crucial role in the aggressiveness of salivary gland tumors as this cytokine was expressed only in the malignant group with high expression associated with high-grade malignancy.

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Mediators of extracellular matrix degradation and inflammation: A new team of possible biomarkers for oral squamous cell carcinoma stage

Cited by 8 publications

References 49 publications

Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer

Interplay Between Immune and Cancer-Associated Fibroblasts: A Path to Target Metalloproteinases in Penile Cancer

The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

Evaluation of CD44s, CD44v6, CXCR2, CXCL1, and IL-1β in Benign and Malignant Tumors of Salivary Glands

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