Recent studies have demonstrated a relationship between oral bacteria and systemic inflammation. Endothelial cells (ECs), which line blood vessels, control the opening and closing of the vascular barrier and contribute to hematogenous metastasis; however, the role of oral bacteria‐induced vascular inflammation in tumor metastasis remains unclear. In this study, we examined the phenotypic changes in vascular ECs following Streptococcus mutans (S. mutans) stimulation in vitro and in vivo. The expression of molecules associated with vascular inflammation and barrier‐associated adhesion was analyzed. Tumor metastasis was evaluated after intravenous injection of S. mutans in murine breast cancer hematogenous metastasis model. The results indicated that S. mutans invaded the ECs accompanied by inflammation and NF‐κB activation. S. mutans exposure potentially disrupts endothelial integrity by decreasing vascular endothelial (VE)‐cadherin expression. The migration and adhesion of tumor cells were enhanced in S. mutans‐stimulated ECs. Furthermore, S. mutans‐induced lung vascular inflammation promoted breast cancer cell metastasis to the lungs in vivo. The results indicate that oral bacteria promote tumor metastasis through vascular inflammation and the disruption of vascular barrier function. Improving oral hygiene in patients with cancer is of great significance in preventing postoperative pneumonia and tumor metastasis.

Thrombosis is a well‐known cardiovascular disease (CVD) complication that has caused death in many patients with cancer. Oral bacteria have been reported to contribute to systemic diseases, including CVDs, and tumor metastasis. However, whether oral bacteria‐induced thrombosis induces tumor metastasis remains poorly understood. In this study, the cariogenic oral bacterium Streptococcus mutans was used to examine thrombosis in vitro and in vivo. Investigation of tumor metastasis to the lungs was undertaken by intravenous S. mutans implantation using a murine breast cancer metastasis model. The results indicated that platelet activation, aggregation, and coagulation were significantly altered in S. mutans‐stimulated endothelial cells (ECs), with elevated neutrophil migration, thereby inducing thrombosis formation. Streptococcus mutans stimulation significantly enhances platelet and tumor cell adhesion to the inflamed ECs. Furthermore, S. mutans‐induced pulmonary thrombosis promotes breast cancer cell metastasis to the lungs in vivo, which can be reduced by using aspirin, an antiplatelet drug. Our findings indicate that oral bacteria promote tumor metastasis through thrombosis formation. Oral health management is important to prevent CVDs, tumor metastasis, and their associated death.

Recent studies reported the role of Porphyromonas gingivalis (P. g) in promoting oral squamous cell carcinoma (OSCC) progression. However, the molecular mechanism remains unclear. P. g-OMVs were isolated using ultracentrifugation method and characterized by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). CCK-8, migration, invasion, Quantitative real-time Polymerase Chain Reaction (qRT-PCR) and immunocytochemistry assays were performed to evaluate the effect of P. g-OMVs on tumor cells’ proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and ferroptosis in vitro. Western blot was performed to study the phosphorylation of transcription factor nuclear factor kappa B (NF-κB). In vivo, the effect of P. g-OMVs on the growth of OSCC was evaluated using a xenograft tumor model, followed by hematoxylin and eosin and immunohistochemistry staining. TEM and NTA demonstrated that P. g-OMVs have a vesicular structure with a particle size of around 118 nm. Compared to the control group, P. g-OMVs significantly enhance the proliferation, migration, and invasion of tumor cells. In addition, P. g-OMVs promote the EMT of OSCC cells, which can be attenuated by ferroptosis activator erastin. Moreover, P. g-OMVs inhibit feroptosis of OSCC by activating NF-κB signaling. In vivo, P. g-OMVs significantly enhance tumor growth of OSCC. Inhibition of NF-κB could significnatly reduce the growth of OSCC, which can be further rescued using ferroptosis inhibitor Ferrostain-1. P. g-OMVs promote OSCC progression by modulating the ferroptosis-related EMT through NF-κB signaling.

Immunotherapy mediated by recombinant antibodies is an effective therapeutic strategy for a variety of cancers. In a previous study, we demonstrated that the fibroblast growth factor 1 (FGF‐1)‐specific recombinant antibody scFv1C9 arrests the cell cycle at the G0/G1 transition by blocking the intracrine FGF‐1 pathway in breast cancer cells. Here, we further show that the overexpression of scFv1C9 in MCF‐7 and MDA‐MB‐231 breast cancer cells by lentiviral infection resulted in decreased tumourigenicity, tumour growth and lung metastasis through FGF‐1 neutralization. We found that scFv1C9 resulted in the up‐regulation of p21, which in turn inhibited the expression of CDK2 and blocked cell cycle progression. To explore the potential role of scFv1C9 in vivo, we delivered the gene into solid tumours by electroporation, which resulted in significant inhibition of tumour growth. In tumour tissue sections, immunohistochemical staining of the cellular proliferation marker Ki‐67 and the microvessel marker CD31 showed a reduction in the proliferative index and microvessel density, respectively, upon expression of scFv1C9 compared with the appropriate controls. Thus, our data indicate a central role for scFv1C9 in blocking the intracrine pathway of FGF‐1, therefore, scFv1C9 could be developed in an effective therapeutic for breast cancer.

Background Oral squamous cell carcinoma (OSCC) is the commonest invasive malignancy in the head and neck regions, with a worse prognosis. Recent studies revealed the role of nuclear receptor coactivator 7 (NCOA7) in promoting tumorigenesis. However, the molecular mechanism remains unclear. Methods Human OSCC tissues were collected and stained with H&E and NCOA7. The expression of NCOA7 in both normal and tumor tissues was compared, along with a correlation analysis with clinicopathological parameters. In vitro, NCOA7 was knocked down, and the proliferation, migration, invasion, and ferroptosis were evaluated using CCK-8, transwell and 3D spheroid migration and invasion assays, qRT-PCR, western blot, and immunocytochemistry. The effects of NCOA7 on intracellular reactive oxygen species (ROS) and ferroptosis in OSCC cells were investigated under the treatment of antioxidants N-Acetyl-L-cysteine (NAC), ferroptosis inhibitors deferoxamine mesylate (DFO) and ferrostatin-1 (Fer-1), and ferroptosis inducers erastin. The Institutional Ethics Committee approved all clinical protocols. Results Significantly high expression of NCOA7 was found in OSCC tissues and was linked to the advancement of OSCC. In vitro, NCOA7 knockdown statistically reduced the proliferation, migration, and invasion of OSCC cells, which could be rescued using NAC or Fer-1. Moreover, NCOA7 knockdown cells exhibited significantly high levels of ROS and ferroptosis, which could be reversed using NAC or DFO or Fer-1. Further investigations revealed that inhibiting ROS in OSCC cells reduced ferroptosis, while erastin could reverse its inhibitory effect. Conclusions NCOA7 promotes OSCC progression by inhibiting ferroptosis through ROS signaling. NCOA7 might be a new therapeutic target for OSCC.