Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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TJP1 Contributes to Tumor Progression through Supporting Cell-Cell Aggregation and Communicating with Tumor Microenvironment in Leiomyosarcoma

  • Lee, Eun-Young (Division of Translational Science, Research Institute, National Cancer Center) ;
  • Kim, Minjeong (Division of Translational Science, Research Institute, National Cancer Center) ;
  • Choi, Beom K. (Biomedicine Production Branch, Research Institute, National Cancer Center) ;
  • Kim, Dae Hong (Division of Convergence Technology, Research Institute, National Cancer Center) ;
  • Choi, Inho (Department of Medical Biotechnology, Yeungnam University) ;
  • You, Hye Jin (Division of Translational Science, Research Institute, National Cancer Center)
  • Received : 2021.05.18
  • Accepted : 2021.09.14
  • Published : 2021.11.30
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Abstract

Leiomyosarcoma (LMS) is a mesenchymal malignancy with a complex karyotype. Despite accumulated evidence, the factors contributing to the development of LMS are unclear. Here, we investigated the role of tight-junction protein 1 (TJP1), a membrane-associated intercellular barrier protein during the development of LMS and the tumor microenvironment. We orthotopically transplanted SK-LMS-1 cells and their derivatives in terms of TJP1 expression by intramuscular injection, such as SK-LMS-1 Sh-Control cells and SK-LMS-1 Sh-TJP1. We observed robust tumor growth in mice transplanted with LMS cell lines expressing TJP1 while no tumor mass was found in mice transplanted with SK-LMS-1 Sh-TJP1 cells with silenced TJP1 expression. Tissues from mice were stained and further analyzed to clarify the effects of TJP1 expression on tumor development and the tumor microenvironment. To identify the TJP1-dependent factors important in the development of LMS, genes with altered expression were selected in SK-LMS-1 cells such as cyclinD1, CSF1 and so on. The top 10% of highly expressed genes in LMS tissues were obtained from public databases. Further analysis revealed two clusters related to cell proliferation and the tumor microenvironment. Furthermore, integrated analyses of the gene expression networks revealed correlations among TJP1, CSF1 and CTLA4 at the mRNA level, suggesting a possible role for TJP1 in the immune environment. Taken together, these results imply that TJP1 contributes to the development of sarcoma by proliferation through modulating cell-cell aggregation and communication through cytokines in the tumor microenvironment and might be a beneficial therapeutic target.

Keywords

Acknowledgement

We thank Mi Sun Park (V.M.D.) and Bo Ra Kim (V.M.D.) of Animal Laboratory (National Cancer Center) and Dr. Se Hun Kang and colleagues of National Cancer Center Animal Molecular Imaging Team, Dr. Eun Kyung Hong, professional pathologist, Department of Pathology, National Cancer Center Hospital, Dr. Jong Kwang Kim of NCC Omics Core Center for their expert assistance and helpful suggestions. We also thank the NCC sarcoma research group (National Cancer Center) for their advice. This research was funded by National Cancer Center grant NCC-1710252 (to H.J.Y.), NCC-1810865 (to H.J.Y.), NCC2110521 (to H.J.Y.) and by the Korean Medical Device Development Fund Grant funded by the Korean Government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) NTIS-202012E12-02 (to D.H.K.).

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