NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B
Human hepatocellular carcinoma (HCC) is the most common and even worse at prognosis. The patients with HCC which accompanied by other diseases, such as cirrhosis, can be limited in various treatments, such as chemotherapy, not HCC patients without other diseases. NLRP3 inflammasome plays an importan...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9285 |
| _version_ | 1797521383208517632 |
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| author | Hwan Hee Lee Dongoh Kim Joohee Jung Hyojeung Kang Hyosun Cho |
| author_facet | Hwan Hee Lee Dongoh Kim Joohee Jung Hyojeung Kang Hyosun Cho |
| author_sort | Hwan Hee Lee |
| collection | DOAJ |
| description | Human hepatocellular carcinoma (HCC) is the most common and even worse at prognosis. The patients with HCC which accompanied by other diseases, such as cirrhosis, can be limited in various treatments, such as chemotherapy, not HCC patients without other diseases. NLRP3 inflammasome plays an important role in the innate immune response, but emerging evidence has indicated that the NLRP3 inflammasome is implicated in all stages of cancer development. Various cells express NLRP3 protein through the autocrine or paracrine signaling in their environment, but NK cells do not. The expanding evidence shows that patients who suffer from liver cancers have a low frequency of natural killer (NK) cells, and the function of these cells is also impaired. Thus, we examined how the expression of NLRP3 in HCC cells affects cancer surveillance by NK cells in a state of a co-culture of both cells. When the expression of NLRP3 in HCC cells was ablated, MICA/B on the surface of HCC cells was upregulated through the lowered expression of matrix metalloproteinase. The expression of MICA on the surface of HCC cells interacted with the NKG2D receptor on NK-92 cells, which led to NK cytotoxicity. Furthermore, in a xenograft mice model, NLRP3 KO HCC cells delayed tumor development and metastasis as well as increased the sensitivity to NK cell cytotoxicity. Taken together, NLRP3 KO in HCC could enhance NK immunosurveillance through an interaction of NKG2D-MICA. |
| first_indexed | 2024-03-10T08:11:49Z |
| format | Article |
| id | doaj.art-901121953de64244a72980d933e98970 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:11:49Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-901121953de64244a72980d933e989702023-11-22T10:40:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217928510.3390/ijms22179285NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/BHwan Hee Lee0Dongoh Kim1Joohee Jung2Hyojeung Kang3Hyosun Cho4Department of Pharmacy, Duksung Women’s University, Seoul 01369, KoreaDuksung Innovative Drug Center, Duksung Women’s University, Seoul 01369, KoreaDepartment of Pharmacy, Duksung Women’s University, Seoul 01369, KoreaVessel-Organ Interaction Research Center, VOICE (MRC), Cancer Research Institute, College of Pharmacy, Kyungpook National University, Daegu 41566, KoreaDepartment of Pharmacy, Duksung Women’s University, Seoul 01369, KoreaHuman hepatocellular carcinoma (HCC) is the most common and even worse at prognosis. The patients with HCC which accompanied by other diseases, such as cirrhosis, can be limited in various treatments, such as chemotherapy, not HCC patients without other diseases. NLRP3 inflammasome plays an important role in the innate immune response, but emerging evidence has indicated that the NLRP3 inflammasome is implicated in all stages of cancer development. Various cells express NLRP3 protein through the autocrine or paracrine signaling in their environment, but NK cells do not. The expanding evidence shows that patients who suffer from liver cancers have a low frequency of natural killer (NK) cells, and the function of these cells is also impaired. Thus, we examined how the expression of NLRP3 in HCC cells affects cancer surveillance by NK cells in a state of a co-culture of both cells. When the expression of NLRP3 in HCC cells was ablated, MICA/B on the surface of HCC cells was upregulated through the lowered expression of matrix metalloproteinase. The expression of MICA on the surface of HCC cells interacted with the NKG2D receptor on NK-92 cells, which led to NK cytotoxicity. Furthermore, in a xenograft mice model, NLRP3 KO HCC cells delayed tumor development and metastasis as well as increased the sensitivity to NK cell cytotoxicity. Taken together, NLRP3 KO in HCC could enhance NK immunosurveillance through an interaction of NKG2D-MICA.https://www.mdpi.com/1422-0067/22/17/9285natural killer (NK) cellhepatocellular carcinoma (HCC)NLRP3MICA/Bxenograft model |
| spellingShingle | Hwan Hee Lee Dongoh Kim Joohee Jung Hyojeung Kang Hyosun Cho NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B International Journal of Molecular Sciences natural killer (NK) cell hepatocellular carcinoma (HCC) NLRP3 MICA/B xenograft model |
| title | NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B |
| title_full | NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B |
| title_fullStr | NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B |
| title_full_unstemmed | NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B |
| title_short | NLRP3 Deficiency in Hepatocellular Carcinoma Enhances Surveillance of NK-92 through a Modulation of MICA/B |
| title_sort | nlrp3 deficiency in hepatocellular carcinoma enhances surveillance of nk 92 through a modulation of mica b |
| topic | natural killer (NK) cell hepatocellular carcinoma (HCC) NLRP3 MICA/B xenograft model |
| url | https://www.mdpi.com/1422-0067/22/17/9285 |
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