Type I collagen degradation by invasive oral squamous cell carcinoma

Oral Oncology ◽  
2000 ◽  
Vol 36 (4) ◽  
pp. 365-372 ◽  
Author(s):  
B Ziober
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jia-Yi Zhang ◽  
Wei-Wen Zhu ◽  
Meng-Yao Wang ◽  
Run-Dong Zhai ◽  
Qiong Wang ◽  
...  

Abstract Background Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs’ function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression. Methods Multiple immunohistochemistry (IHC) staining was performed to detect the correlation of CAFs and LOX in the stroma of OSCC specimens, as well as the correlation with clinicopathological parameters and prognosis. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing and transwell assay. CAFs were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the progression of OSCC. Moreover, we used focal adhesion kinase (FAK) phosphorylation inhibitors to explored whether the increase in matrix stiffness promote the progression of OSCC through activating FAK phosphorylation pathway. Results LOX was colocalized with CAFs in the stroma of OSCC tissues, and its expression was significantly related to the degree of malignant differentiation and poor prognosis in OSCC. LOX was highly expressed in CAFs, and its knockdown impaired the proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, CAFs-derived LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway. Conclusions Our findings suggest that CAFs highly express LOX in the stroma of OSCC and can remodel the matrix collagen microenvironment, and the increase in matrix stiffness mediated by CAFs-derived LOX promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC.


2021 ◽  
Author(s):  
Jia-Yi Zhang ◽  
Wei-Wen Zhu ◽  
Meng-Yao Wang ◽  
Run-Dong Zhai ◽  
Qiong Wang ◽  
...  

Abstract Background: Cancer-associated fibroblasts (CAFs), the most abundant cells in the tumor microenvironment, have prominent roles in the development of solid tumors as stromal targets. However, the underlying mechanism of CAFs’ function in oral squamous cell carcinoma (OSCC) development remains unclear. Here, we investigated the role of lysyl oxidase (LOX) expression in CAFs in tumor stromal remodeling and the mechanism of its effect on OSCC progression. Methods: Immunohistochemistry was performed to detect the expression and correlation of the α - SMA and LOX in OSCC specimens, as well as the correlation with clinicopathological parameters. The expression of LOX in CAFs were detected by RT-qPCR and western blot. The effects of LOX in CAFs on the biological characteristics of OSCC cell line were investigated using CCK-8, wound-healing, Transwell migration and invasion assay. Next, CAFs cells were co-cultured with type I collagen in vitro, and collagen contraction test, microstructure observation and rheometer were used to detect the effect of CAFs on remodeling collagen matrix. Then, collagen with different stiffness were established to investigate the effect of matrix stiffness on the invasion and EMT of OSCC cells. Moreover, we explored whether the increase of matrix stiffness promote the progress of OSCC through activating focal adhesion kinase (FAK) phosphorylation pathway.Results: In OSCC specimens, α-SMA, the specific markers of CAFs, and LOX were highly expressed in tumor stromal tissues, and they were significantly correlated with the degree of malignant differentiation. LOX was highly expressed in CAFs, and its knockdown impaired proliferation, migration, invasion and EMT process of OSCC cells. The expression of LOX in CAFs can catalyze collagen crosslinking and increase matrix stiffness. Furthermore, LOX-mediated increase in collagen stiffness induced morphological changes and promoted invasion and EMT process in OSCC cells by activating FAK phosphorylation pathway. Conclusions: Our findings suggest that CAFs highly express LOX in OSCC and can remodel the matrix collagen microenvironment, and an increase in LOX-mediated matrix stiffness promotes OSCC development through FAK phosphorylation pathway. Thus, LOX may be a potential target for the early diagnosis and therapeutic treatment of OSCC.


2016 ◽  
Vol 07 (07) ◽  
pp. 255-263 ◽  
Author(s):  
Masahiko Morioka ◽  
Mai Hazekawa ◽  
Tomoyo Kawakubo-Yasukochi ◽  
Takuya Nishinakagawa ◽  
Seiji Nakamura ◽  
...  

2020 ◽  
Vol 15 ◽  
Author(s):  
Yong Mi ◽  
Na Li ◽  
Qing Li ◽  
Yang Shi ◽  
Congcong Zhang ◽  
...  

Background: Oral squamous cell carcinoma (OSCC) had been the sixth most common cancer worldwide. Emerging studies showed long non-coding RNAs played a key role in human cancers. However, the molecular mechanisms underlying the initiation and progression of OSCC remained to be further explored Objective: The present study aimed to identify differentially expressed lncRNAs and mRNAs in OSCC. Methods: GSE30784 was analyzed to identify differentially expressed lncRNAs and mRNAs in OSCC. Protein-protein interaction network and co-expression network analysis were performed to reveal the potential roles of OSCC related mRNAs and lncRNAs Results: In present study, we identified 21 up-regulated lncRNAs and 54 down-regulated lncRNAs in OSCC progression. Next we constructed a lncRNA related co-expression network in OSCC, which included 692 mRNAs and 2193 edges. Bioinformatics analysis showed lncRNAs were widely co-expressing with regulating type I interferon signaling pathway, extracellular matrix organization, collagen catabolic process, immune response, ECM-receptor interaction, Focal adhesion, and PI3K-Akt signaling pathway. A key network, included lncRNA C5orf66-AS1, C21orf15, LOC100506098, PCBP1-AS1, LOC284825, OR7E14P, HCG22, and FLG-AS1, were found to be involved in the regulation of immune response to tumor cell, Golgi calcium ion transport, negative regulation of vitamin D receptor signaling pathway, glycerol-3-phosphate catabolic process. Moreover, we found showed higher expression of CYP4F29P, PCBP1-AS1, HCG22, and C5orf66-AS1were associated with shorter overall survival time in OSCC samples Conclusions: We thought our analysis could provide novel insights to explore the potential mechanisms underlying OSCC progression


2004 ◽  
Vol 204 (3) ◽  
pp. 333-339 ◽  
Author(s):  
L�on CLT van Kempen ◽  
Jos Rijntjes ◽  
An Claes ◽  
Willeke AM Blokx ◽  
Marie-Jeanne P Gerritsen ◽  
...  

Cancer ◽  
2002 ◽  
Vol 94 (4) ◽  
pp. 940-949 ◽  
Author(s):  
Yoshihiro Nabeya ◽  
Hideaki Shimada ◽  
Shinichi Okazumi ◽  
Hisahiro Matsubara ◽  
Yoshio Gunji ◽  
...  

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