Porphyromonas gingivalis Promotes Oral Squamous Cell Carcinoma Progression in an Immune Microenvironment

2020 ◽  
Vol 99 (6) ◽  
pp. 666-675 ◽  
Author(s):  
L. Wen ◽  
W. Mu ◽  
H. Lu ◽  
X. Wang ◽  
J. Fang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Porphyromonas Gingivalis ◽  
Squamous Cell ◽  
Oral Lesions ◽  
Potential Candidate

Increasing evidence has revealed a significant association between microorganisms and oral squamous cell carcinoma (OSCC). Porphyromonas gingivalis, the keystone pathogen in chronic periodontitis, is considered an important potential etiologic agent of OSCC, but the underlying immune mechanisms through which P. gingivalis mediates tumor progression of the oral cancer remain poorly understood. Our cohort study showed that the localization of P. gingivalis in tumor tissues was related to poor survival of patients with OSCC. Moreover, P. gingivalis infection increased oral lesion multiplicity and size and promoted tumor progression in a 4-nitroquinoline-1 oxide (4NQO)–induced carcinogenesis mouse model by invading the oral lesions. In addition, CD11b+ myeloid cells and myeloid-derived suppressor cells (MDSCs) showed increased infiltration of oral lesions. Furthermore, in vitro observations showed that MDSCs accumulated when human-derived dysplastic oral keratinocytes (DOKs) were exposed to P. gingivalis, and CXCL2, CCL2, interleukin (IL)–6, and IL-8 may be potential candidate genes that facilitate the recruitment of MDSCs. Taken together, our findings suggest that P. gingivalis promotes tumor progression by generating a cancer-promoting microenvironment, indicating a close relationship among P. gingivalis, tumor progression of the oral cancer, and immune responses.

Inhibition of Angiogenesis and Tumor Progression of Mk-0429, an Integrin Αvβ3 Antagonist, on Oral Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Takayuki Nakagawa ◽  
Kouji Ohta ◽  
Takako Naruse ◽  
Miyuki Sakuma ◽  
Satoshi Okuda ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tube Formation ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeIntegrin αvβ3 is an essential molecule for tumor angiogenesis. This study aimed to investigate the anti-tumor effect of MK-0429, an integrin αvβ3 antagonist, on oral squamous cell carcinoma (OSCC) through its inhibitory effect on angiogenesis.MethodsIn this study, we investigated the effect of MK-0429 on cellular function and angiogenesis in vitro with the use of an immortalized human umbilical vein endothelial cell, HUEhT-1, which is immortalized by the electroporatic transfection of hTERT. The effect of MK-0429 on the integrin αvβ3 signaling pathway was examined by FAK and ERK 1/2 phosphorylation. The anti-angiogenic effect of MK-0429 was evaluated by in vitro tube formation assay. The anti-tumor effect on OSCC was assessed by administrating MK-0429 to mouse oral cancer xenografts.ResultsMK-0429 inhibited cell proliferation, migration, and adhesion of HUEhT-1 in a dose-dependent manner. FAK and ERK phosphorylation were significantly blocked by MK-0429 treatment. Tube formation was suppressed by MK-0429 in dose-dependent manner. Tumor progression was significantly suppressed by MK-0429 administration in mouse oral cancer xenografts. Histological study revealed that MK-0429 decreased tumor vascularization.ConclusionThese results indicated integrin αvβ3 as a therapeutic target for OSCC and suggested that MK-0429 might be clinically applicable as an anti-tumor agent with potent antiangiogenic activity.

scholarly journals Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wen Chen ◽  
Chenzhou Wu ◽  
Yafei Chen ◽  
Yuhao Guo ◽  
Ling Qiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum Stress ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Ceramide Synthase

AbstractC18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma. However, the function of ceramide synthase 1, a key enzyme in C18 ceramide synthesis, in oral squamous cell carcinoma is still unclear. The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer. In this study, we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines. In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide, ceramide synthase 1 knockout was associated with the severity of oral malignant transformation. Immunohistochemical studies showed significant upregulation of PCNA, MMP2, MMP9, and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area. In addition, ceramide synthase 1 knockdown promoted cell proliferation, migration, and invasion in vitro. Overexpression of CERS1 obtained the opposite effect. Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation. Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation. In addition, mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance. Taken together, our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.

scholarly journals NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression

2021 ◽  
Vol 22 (20) ◽  
pp. 11108
Author(s):  
Sarah Adriana Scuderi ◽  
Giovanna Casili ◽  
Rossella Basilotta ◽  
Marika Lanza ◽  
Alessia Filippone ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Squamous Cell ◽  
Nlrp3 Inflammasome ◽  
P53 Expression

Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.

scholarly journals Differences in the expression of caveolin-1 isoforms in cancer-associated and normal fibroblasts of patients with oral squamous cell carcinoma

2021 ◽  
Author(s):  
S. Kaya ◽  
Nadine Wiesmann ◽  
J. Goldschmitt ◽  
M. Krüger ◽  
B. Al-Nawas ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Scaffolding Protein ◽  
Caveolin 1 ◽  
Tumor Stages

Abstract Objectives For many years, tumor development has been viewed as a cell-autonomous process; however, today we know that the tumor microenvironment (TME) and especially cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression. Caveolin-1 (Cav-1) is a scaffolding protein which is involved in several cancer-associated processes as important component of the caveolae. Our goal was to shed light on the expression of the two different isoforms of Cav-1 in normal fibroblasts (NFs) and CAFs of patients with oral squamous cell carcinoma (OSCC). Materials and methods Fibroblasts from normal mucosa and CAFs were isolated and propagated in vitro. Gene expression of the different Cav-1 isoforms was assessed via quantitative real-time PCR (qPCR) and supplemented by protein expression analysis. Results We could show that the Cav-1β isoform is more highly expressed in NFs and CAFs compared to Cav-1α. Furthermore, the different Cav-1 isoforms tended to be differently expressed in different tumor stages. However, this trend could not be seen consistently, which is in line with the ambiguous role of Cav-1 in tumor progression described in literature. Western blotting furthermore revealed that NFs and CAFs might differ in the oligomerization profile of the Cav-1 protein. Conclusion These differences in expression of Cav-1 between NFs and CAFs of patients with OSCC confirm that the protein might play a role in tumor progression and is of interest for further analyses. Clinical relevance Our findings support a possible role of the two isoforms of Cav-1 in the malignant transformation of OSCC.

scholarly journals Serum Levels of Interleukin-6 and Titers of Antibodies against Porphyromonas gingivalis Could Be Potential Biomarkers for the Diagnosis of Oral Squamous Cell Carcinoma

2019 ◽  
Vol 20 (11) ◽  
pp. 2749 ◽  
Author(s):  
Dae-Gun Park ◽  
Bok Hee Woo ◽  
Byung-Joo Lee ◽  
Sanggyeong Yoon ◽  
Youngseuk Cho ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Serum Level ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Porphyromonas Gingivalis ◽  
Squamous Cell ◽  
Interleukin 6 ◽  
Serum Levels ◽  
Periodontal Pathogens

It has been suggested that Porphyromonas gingivalis (P. gingivalis), a keystone pathogen in chronic periodontitis, is associated with a variety of cancers, including oral cancer. Recently, studies have shown the effects of persistent exposure to P. gingivalis on the promotion of tumorigenic properties of oral epithelial cells, suggesting that chronic P. gingivalis infection is a potential risk factor for oral cancer. On the other hand, Fusobacterium nucleatum (F. nucleatum), one of the major periodontal pathogens, has emerged as an important factor in the colon cancer progression. Here, we investigated the diagnostic potential of serum immunoglobulin G antibody against periodontal pathogens, P. gingivalis and F. nucleatum, and serum IL-6 for oral squamous cell carcinoma (OSCC). An enzyme-linked immunosorbent assay (ELISA) was used to determine and compare the serum levels of interleukin 6 (IL-6), F. nucleatum IgG, and P. gingivalis IgG in 62 OSCC patients with 46 healthy controls. The serum levels of P. gingivalis IgG and IL-6 were higher in OSCC patients than in non-OSCC controls, and the difference was statistically significant. In addition, a high serum level of IL-6 was associated with a worse prognosis in OSCC patients. Thus, P. gingivalis IgG and IL-6 could be utilized as potential serum biomarkers for the diagnosis of OSCC, and the serum level of IL-6 contributes to improved prognostic performance.

scholarly journals Oral Administration of Porphyromonas gingivalis, a Major Pathogen of Chronic Periodontitis, Promotes Resistance to Paclitaxel in Mouse Xenografts of Oral Squamous Cell Carcinoma

2019 ◽  
Vol 20 (10) ◽  
pp. 2494 ◽  
Author(s):  
Jae Min Song ◽  
Bok Hee Woo ◽  
Ji Hye Lee ◽  
Sanggyeong Yoon ◽  
Youngseuk Cho ◽  
...  
Keyword(s):  
Growth Rate ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Porphyromonas Gingivalis ◽  
Squamous Cell ◽  
Chronic Periodontitis ◽  
Tumor Growth Rate

Chemotherapy is not a first-line therapy for oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer, because most OSCC shows resistance to chemotherapeutic reagents. Inflammatory signals are suggested to be associated with chemoresistance as well as carcinogenesis in many different cancers, and thus chronic periodontitis, the most common chronic inflammatory disease of the oral cavity, could modulate responsiveness to chemotherapeutic agents used against oral cancer. This study was performed to define the role of chronic periodontitis in oral cancer progression and to determine the responsiveness of oral cancer to a chemotherapeutic reagent. First, we quantified the tumor growth rate and changes in serum cytokine profiles of mice administered Porphyromonas gingivalis, a major pathogen of chronic periodontitis. Compared with uninfected mice, the mice that were chronically administered P. gingivalis showed increased resistance to paclitaxel and a decreased tumor growth rate. In addition, P. gingivalis-treated mice exhibited higher serum levels of interleukin-6 (IL-6) than uninfected mice. Furthermore, the sensitivity of tumor xenografts to paclitaxel in mice administered P. gingivalis was dramatically increased when the mice were administered ibuprofen, an anti-inflammatory drug which supports the modulatory effect of periodontal pathogen-induced inflammation in chemoresistance.

scholarly journals Zymosan Promotes Proliferation, Candida albicans Adhesion and IL-1β Production of Oral Squamous Cell Carcinoma In Vitro

2020 ◽  
Author(s):  
XU CHEN ◽  
Qingqiong Luo ◽  
Jieying Ding ◽  
Meng Yang ◽  
Ruiyang Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Wall ◽  
Candida Albicans ◽  
Cell Adhesion ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Adhesion Assay

Abstract Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC), and the effect of zymosan (ZYM), a component of the yeast cell wall, on oral cancer remains unclear. The CCK-8 proliferation assay was performed to evaluate the effect of ZYM on the proliferation of the OSCC cell lines WSU-HN4, WSU-HN6 and CAL27, and the potential mechanism was explored by quantitative real-time PCR, immunofluorescence assay and western blot. A cell adhesion assay was conducted to determine the adhesion of Candida albicans to OSCC cells, and the expression of related genes, including TLR2 , MyD88 , NLRP3 , ASC , Caspase-1 and IL-1β , and proteins, including TLR2, MyD88, NF-κB p65, p-NF-κB p65 and E-cadherin was determined. Additionally, the pro-inflammatory cytokines including IL-6, IL-8, TNF-α and IL-1β produced by OSCC cells were detected using a chemiluminescence immunoassay (CLIA). In the current study, the CCK-8 assay showed that ZYM promoted the proliferation of WSU-HN4, WSU-HN6 and CAL27 cells via the TLR2/MyD88 pathway. The cell adhesion assay showed that the number of C. albicans cells per field significantly increased in ZYM-treated OSCC cells compared to controls. When treated with ZYM, OSCC cells secreted significantly more pro-inflammatory cytokine IL-1β, which could enhance inflammation in oral cancer microenvironment. In conclusion, ZYM from the fungal cell wall promotes the proliferation, C. albicans adhesion and IL-1β production in OSCC, as demonstrated by in vitro experiments.

scholarly journals Zymosan Promotes Proliferation, Candida albicans Adhesion and IL-1β Production of Oral Squamous Cell Carcinoma In Vitro

2020 ◽  
Author(s):  
XU CHEN ◽  
Qingqiong Luo ◽  
Jieying Ding ◽  
Meng Yang ◽  
Ruiyang Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Wall ◽  
Candida Albicans ◽  
Cell Adhesion ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Adhesion Assay

Abstract Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC), and the effect of zymosan, a component of yeast cell wall, on oral cancer remains unclear. Cell proliferation assay was performed with CCK-8 to evaluate the effect of zymosan on proliferation of OSCC cell lines including WSU-HN4, WSU-HN6 and CAL-27, and potential mechanism was explored by quantitative real-time PCR, immunofluorescence assay and western blot. Cell adhesion assay was conducted to determine the adhesion of Candida albicans to OSCC cells, and related gene expression and protein was detected. Also, the proinflammatory cytokines including IL-6, IL-8, TNF-α and IL-1β from OSCC cells were determined by ELISA. In current study, zymosan (ZYM) promotes proliferation of OSCC cell lines including WSU-HN4, WSU-HN6 and CAL-27 by CCK-8 assay via TLR2/MyD88 pathway. By cell adhesion assay, the number of Candida albicans per oil field significantly increased in ZYM-treated OSCC cells compared to controls. When treated with zymosan, OSCC cells secreted significantly more pro-inflammatory cytokine IL-1β, which could enhance inflammation in oral cancer microenvironment. Zymosan from fungi cell wall promotes proliferation, Candida albicans adhesion and IL-1β production of oral squamous cell carcinoma by in-vitro experiments.

scholarly journals Candida albicans Enhances the Progression of Oral Squamous Cell Carcinoma In Vitro and In Vivo

mBio ◽  
2022 ◽  
Author(s):  
Máté Vadovics ◽  
Jemima Ho ◽  
Nóra Igaz ◽  
Róbert Alföldi ◽  
Dávid Rakk ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Candida Albicans ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Healthy Individuals ◽  
Oral Cancer Patients

Oral squamous cell carcinoma (OSCC) is a serious health issue worldwide that accounts for 2% to 4% of all cancer cases. Previous studies have revealed a higher yeast carriage and diversity in oral cancer patients than in healthy individuals.

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