Extracellular vesicles from Fusobacterium nucleatum: roles in the malignant phenotypes of gastric cancer

ABSTRACT

The increase of the Fusobacterium nucleatum level has been previously identified in various cancers including gastric cancer (GC), but how the F. nucleatum exerts its carcinogenic role in GC remains unclear. Several studies revealed that F. nucleatum contributes to cancer progression via its secretion of extracellular vehicles (EVs). Hence, it’s designed to reveal the influence of F. nucleatum-derived EVs (Fn-EVs) in GC progression. The tumor and adjacent tissues were collected from 30 GC patients, and the abundance of F. nucleatum was found to be highly expressed in tumor samples. The ultracentrifugation was employed to isolate EVs from F. nucleatum and Escherischia coli (E. coli), which were labeled Fn-EVs and E. coli-EVs, respectively. After treating GC cells with Fn-EVs and E. coli-EVs, cell counting kit 8, colony formation, wound healing as well as transwell assay were performed, which revealed that Fn-EVs effectively enhanced oxaliplatin resistance, and facilitated cell proliferation, migration, invasion, and stemness in GC cells while E. coli-EVs exert no significant effect on GC cells. Besides, the stemness and DNA repair of GC cells were also enhanced by Fn-EVs, as revealed by the sphere-forming assay and the detection of stemness- and DNA repair-associated proteins by western blotting. In vivo analyses demonstrated that Fn-EVs administration not only promoted GC tumor growth and liver metastasis but also conferred GC tumor resistance to oxaliplatin resistance. This study first revealed the contributive role of F. nucleatum in GC development via Fn-EVs, which provided a better perspective for manipulating F. nucleatum in treating GC patients with malignant phenotypes.

KEYWORDS:

• Gastric cancer
• Fusobacterium nucleatum
• extracellular vesicles

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author contributions

Xiangkun Meng and Fang He designed experiments. Gang Ma and Xu Zhang carried out experiments. Hua Yin and Yu Miao analyzed experimental results. Xiangkun Meng wrote the manuscript. Fang He revised the manuscript. All authors approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2024.2324587

Ethical approval

The study abided by the guidelines of the Helsinki Declaration, was approved through the Ethics Committee of General Hospital of Ningxia Medical University. All animal experiments were approved through the Ethics Committee of General Hospital of Ningxia Medical University and abided by the principles of ARRIVE guidelines.

Informed consent from participants

Informed consent obtained from all patients.

Additional information

Funding

This work was supported by Natural Science Foundation of Ningxia Province [2021AAC03402] and Natural Science Foundation of Ningxia Province [2022A1251].