TGM2 inhibits the proliferation, migration and tumorigenesis of MDCK cells

PLoS One. 2023 Apr 28;18(4):e0285136. doi: 10.1371/journal.pone.0285136. eCollection 2023.

Abstract

Madin-Darby canine kidney (MDCK) cells are one of the main cell lines used for influenza vaccine production due to their high virus yield and low mutation resistance. Due to their high tumorigenicity, the safety of vaccines produced from these cells is controversial. TGM2 is a multifunctional protein that plays an important role in the adhesion and migration of cells and is associated with tumor formation. We found that the expression level of TGM2 was significantly up-regulated in low tumorigenic MDCK cells. We first analyzed TGM2-overexpressed and knockout MDCK cells in vitro. Scratch-wound assay and Transwell chamber experiments showed that TGM2 overexpression significantly inhibited the migration and invasion of MDCK cells and significantly reduced their proliferation. TGM2 knockout significantly enhanced cell migration, invasion, and proliferation. The tumorigenesis results in nude mice were consistent with those in vitro. TGM2 knockout significantly enhanced the tumorigenesis rate of MDCK cells in nude mice. We also investigated the effects of TGM2 gene expression on the replication of the H1N1 influenza A virus in MDCK cells. The results showed that TGM2 induced the negative regulation of H1N1 replication. These findings contribute to a comprehensive understanding of the tumor regulation mechanism and biological functions of TGM2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Cell Proliferation
  • Dogs
  • Influenza A Virus, H1N1 Subtype* / physiology
  • Influenza A virus*
  • Madin Darby Canine Kidney Cells
  • Mice
  • Mice, Nude
  • Protein Glutamine gamma Glutamyltransferase 2 / metabolism

Substances

  • Protein Glutamine gamma Glutamyltransferase 2

Grants and funding

This research was funded and supported by the Fundamental Research Funds for, the National Natural Science Foundation of China (32160164), the Scientific research innovation project of Northwest Minzu University (Yxm2021078), the Scientific research innovation project of Northwest Minzu University (Yxm2021079).