Expressions of extracellular matrix‐remodeling factors in lymph nodes from oral cancer patients

Fujita, Shuichi; Sumi, Misa; Tatsukawa, Eri; Nagano, Kenichi; Katase, Naoki

doi:10.1111/odi.13419

Cited by 11 publications

(6 citation statements)

References 33 publications

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“…Increased fibrinogen deposition was found in tumor-draining LNs compared to control LNs [92]. Furthermore, enhanced production of ECMremodeling factors such as LOX, MT1-MMP and TIMP-1 was detected in metastatic LNs from patients with oral cancer [166]. This was in line with the implication of LOX and MMPs in the liver and lung pre-metastatic niches [167][168][169][170].…”

Section: Ln Extracellular Matrix Remodeling In the Pre-metastatic Nichesupporting

confidence: 65%

The pre-metastatic niche in lymph nodes: formation and characteristics

Gillot

Baudin

Rouaud

et al. 2021

Cell. Mol. Life Sci.

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Lymph node metastasis is a crucial prognostic parameter in many different types of cancers and a gateway for further dissemination to distant organs. Prior to metastatic dissemination, the primary tumor prepares for the remodeling of the draining (sentinel) lymph node by secreting soluble factors or releasing extracellular vesicles that are transported by lymphatic vessels. These important changes occur before the appearance of the first metastatic cell and create what is known as a pre-metastatic niche giving rise to the subsequent survival and growth of metastatic cells. In this review, the lymph node structure, matrix composition and the emerging heterogeneity of cells forming it are described. Current knowledge of the major cellular and molecular processes associated with nodal pre-metastatic niche formation, including lymphangiogenesis, extracellular matrix remodeling, and immunosuppressive cell enlisting in lymph nodes are additionally summarized. Finally, future directions that research could possibly take and the clinical impact are discussed.

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Section: Ln Extracellular Matrix Remodeling In the Pre-metastatic Nichesupporting

confidence: 65%

The pre-metastatic niche in lymph nodes: formation and characteristics

Gillot

Baudin

Rouaud

et al. 2021

Cell. Mol. Life Sci.

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“…MMP14 localises at the surface-membrane expression in OSCC, particularly in the invasive area, and promotes extracellular matrix degradation [28, [29][30][31]. In addition, MMP14 derived from tumour cells activates mesenchymal cells and CAFs in the TME [32][33][34][35][36]. CAFsderived MMP14 releases the matrix, promoting OSCC invasion [28][29][30][31]37].…”

Section: Discussionmentioning

confidence: 99%

“…MMP2, 3, 9, and 14, derived from CAFs and tumour cells in OSCC, are important enzymes for metastasis [38][39][40][41][42]; however, their role in ENE development has not been examined. In vivo studies have revealed that MMP14 in the TME creates a suitable primary and pre-metastatic niche in the LN for tumour survival during epithelial-mesenchymal transition (EMT) [32][33][34][35][36]. This may be a reason for the similar expression pro les of MMP14 at the TSI and ENE sites.…”

Section: Discussionmentioning

confidence: 99%

MMP14 expression levels accurately predict the presence of extranodal extensions in oral squamous cell carcinoma: a retrospective cohort study

Noda

Ishida

Yamaka

et al. 2022

Preprint

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Background: Extranodal extension (ENE) is an adverse prognostic factor for oral squamous cell carcinoma (OSCC), and OSCC patients with ENE require neck dissection. In this study, we developed a novel ENE histology-based pathological predictor using MMP14 expression patterns in small biopsy specimens. Methods: A total of 71 surgically resected tissue, 64 dissected lymph node (LN), and 46 biopsy specimens were collected from 71 OSCC patients. Immunohistochemical analyses of total MMP14 expression in the tumour nest and cancer-associated fibroblasts (CAFs) were performed using the MMP14 co-scoring system (high- or low-risk). The association analysis of MMP14 expression in metastatic LNs was performed with respect to the presence and absence of ENE. Clinicopathological analyses and multivariate examinations were performed to assess the risks of metastasis and ENE presence. The predictive value of ENE was examined. Results: High-risk MMP14 expression was detected in metastatic LN specimens with ENE. MMP14 expression in tumour nests and CAFs and its overexpression at the tumour–stromal interface significantly correlated with the presence of ENE. The MMP14 co-scoring system was an independent risk predictor for ENE, with sensitivity, specificity, and accuracy of over 80% in biopsy samples. Conclusions: The MMP14 co-scoring system accurately predicted ENE presence via immunohistochemical evaluation of small biopsies. This system is a simple, accurate, and inexpensive immunohistochemical approach that can be used in routine pathological diagnosis for effective treatment planning.

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“…High expression of connexin-43 and E-cadherin was also found in the metastatic lymph nodes of gastric cancer [ 153 ]. Furthermore, an increase in enzymes such as lysyl oxidase, membrane type-matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase 1 were associated with ECM degradation in the metastatic lymph nodes of patients with oral cancer [ 154 ]. In contrast, high levels of fibronectin, tenascin-C, and osteopontin in tumor stroma have been shown to be associated with lymph node metastasis [ 155 , 156 ].…”

Section: Metastatic Spread Via Blood and Lymphatic Vesselsmentioning

confidence: 99%

Reprogramming of sentinel lymph node microenvironment during tumor metastasis

Hung

2022

J Biomed Sci

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Metastasis is a major cause of death in patients with cancer. The two main routes for cancer cell dissemination are the blood and lymphatic systems. The underlying mechanism of hematogenous metastasis has been well characterized in the past few decades. However, our understanding of the molecular basis of lymphatic metastasis remains at a premature stage. Conceptually, cancer cells invade into lymphatic capillary, passively move to collecting lymphatic vessels, migrate into sentinel lymph node (SLN;, the first lymph node to which cancer cells spread from the primary tumor), and enter the blood circulatory system via the subclavian vein. Before arriving, cancer cells release specific soluble factors to modulate the microenvironment in SLN to establish a beachhead for successful colonization. After colonization, cancer cells inhibit anti-tumor immunity by inducing the recruitment of regulatory T cell and myeloid-derived suppressor cells, suppressing the function of dendritic cell and CD8+ T cell, and promoting the release of immunosuppressive cytokines. The development of novel strategies to reverse cancer cell-triggered SLN remodeling may re-activate immunity to reduce beachhead buildup and distant metastasis. In addition to being a microanatomic location for metastasis, the SLN is also an important site for immune modulation. Nanotechnology-based approaches to deliver lymph node-tropic antibodies or drug-conjugated nanoparticles to kill cancer cells on site are a new direction for cancer treatment. Conversely, the induction of stronger immunity by promoting antigen presentation in lymph nodes provides an alternate way to enhance the efficacy of immune checkpoint therapy and cancer vaccine. In this review article, we summarize recent findings on the reprogramming of SLN during lymphatic invasion and discuss the possibility of inhibiting tumor metastasis and eliciting anti-tumor immunity by targeting SLN.

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Expressions of extracellular matrix‐remodeling factors in lymph nodes from oral cancer patients

Cited by 11 publications

References 33 publications

The pre-metastatic niche in lymph nodes: formation and characteristics

The pre-metastatic niche in lymph nodes: formation and characteristics

MMP14 expression levels accurately predict the presence of extranodal extensions in oral squamous cell carcinoma: a retrospective cohort study

Reprogramming of sentinel lymph node microenvironment during tumor metastasis

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