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具核梭杆菌感染导致上皮细胞向部分 EMT 表型的转化促进口腔癌细胞的侵袭。

Conversion from epithelial to partial-EMT phenotype by Fusobacterium nucleatum infection promotes invasion of oral cancer cells.

机构信息

Department of Oral Bioscience, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8504, Japan.

Oral Health Care Promotion, Tokushima University Graduate School of Biomedical Sciences, Tokushima, 770-8504, Japan.

出版信息

Sci Rep. 2021 Jul 22;11(1):14943. doi: 10.1038/s41598-021-94384-1.

DOI:10.1038/s41598-021-94384-1
PMID:34294795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8298429/
Abstract

The ability of cancer cells to undergo partial-epithelial mesenchymal transition (p-EMT), rather than complete EMT, poses a higher metastatic risk. Although Fusobacterium nucleatum mainly inhabits in oral cavity, attention has been focused on the F. nucleatum involvement in colorectal cancer development. Here we examined the p-EMT regulation by F. nucleatum in oral squamous cell carcinoma (OSCC) cells. We cultured OSCC cells with epithelial, p-EMT or EMT phenotype with live or heat-inactivated F. nucleatum. Expression of the genes involved in epithelial differentiation, p-EMT and EMT were examined in OSCC cells after co-culture with F. nucleatum by qPCR. Cell growth and invasion of OSCC cells were also examined. Both live and heat-inactivated F. nucleatum upregulated the expression of p-EMT-related genes in OSCC cells with epithelial phenotype, but not with p-EMT or EMT phenotype. Moreover, F. nucleatum promoted invasion of OSCC cells with epithelial phenotype. Co-culture with other strains of bacteria other than Porphyromonas gingivalis did not alter p-EMT-related genes in OSCC cells with epithelial phenotype. F. nucleatum infection may convert epithelial to p-EMT phenotype via altering gene expression in OSCC. Oral hygiene managements against F. nucleatum infection may contribute to reduce the risk for an increase in metastatic ability of OSCC.

摘要

癌细胞发生部分上皮间质转化(p-EMT)而非完全 EMT 时,具有更高的转移风险。虽然具核梭杆菌主要栖息于口腔,但人们已经开始关注其在结直肠癌发展中的作用。在此,我们研究了具核梭杆菌对口腔鳞状细胞癌(OSCC)细胞中 p-EMT 的调控作用。我们分别培养上皮表型、p-EMT 表型和 EMT 表型的 OSCC 细胞,并与活的或热灭活的具核梭杆菌共培养。通过 qPCR 检测 OSCC 细胞与具核梭杆菌共培养后上皮分化、p-EMT 和 EMT 相关基因的表达情况。还检测了 OSCC 细胞的生长和侵袭情况。活的和热灭活的具核梭杆菌均可上调上皮表型 OSCC 细胞中 p-EMT 相关基因的表达,但对 p-EMT 表型或 EMT 表型的 OSCC 细胞无此作用。此外,具核梭杆菌还促进了上皮表型 OSCC 细胞的侵袭。与牙龈卟啉单胞菌以外的其他细菌株共培养不会改变上皮表型 OSCC 细胞中 p-EMT 相关基因的表达。具核梭杆菌感染可能通过改变 OSCC 细胞中的基因表达将上皮表型转化为 p-EMT 表型。针对具核梭杆菌感染的口腔卫生管理可能有助于降低 OSCC 转移能力增强的风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/9656bfe009de/41598_2021_94384_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/be20a995d22d/41598_2021_94384_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/9656bfe009de/41598_2021_94384_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/abb6d7afbaa8/41598_2021_94384_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/025cbc47a0db/41598_2021_94384_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/0d947f347482/41598_2021_94384_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/7505e17645cb/41598_2021_94384_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/02f904e6dfaf/41598_2021_94384_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/8e65412ba1c7/41598_2021_94384_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/be20a995d22d/41598_2021_94384_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a14/8298429/9656bfe009de/41598_2021_94384_Fig8_HTML.jpg

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