NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma
Abstract Background NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CSCs) of squamous cell carcinoma of the head and neck (SCCHN) remain ambi...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2017-09-01
|
| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-017-0589-y |
| _version_ | 1818469850226360320 |
|---|---|
| author | Cong-Fa Huang Lei Chen Yi-Cun Li Lei Wu Guang-Tao Yu Wen-Feng Zhang Zhi-Jun Sun |
| author_facet | Cong-Fa Huang Lei Chen Yi-Cun Li Lei Wu Guang-Tao Yu Wen-Feng Zhang Zhi-Jun Sun |
| author_sort | Cong-Fa Huang |
| collection | DOAJ |
| description | Abstract Background NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CSCs) of squamous cell carcinoma of the head and neck (SCCHN) remain ambiguous. Methods In our study, tissue microarrays, ELISA, sphere-forming assay, colony formation assay and Western blot analysis were performed to evaluate the effect of NLRP3 inflammasome on the development of CSCs in human SCCHN tissue specimen, cell lines, and transgenic mouse SCCHN model. Results The components of NLRP3 inflammasome, namely, NLRP3, ASC, Caspase-1, and IL-18 were correlated with CSCs markers BMI1, ALDH1 and CD44 in human SCCHN specimens. Moreover, NLRP3, Caspase-1, IL-1β, and IL-18 were highly expressed in SCCHN cell lines. NLRP3 inflammasome activated by LPS and ATP promoted sphere-forming and colony formation capacities along with an upregulation of BMI1, ALDH1 and CD44. In addition, NLRP3 inflammasome blockade by NLRP3 inhibitor MCC950 reduced sphere and colony number, also decreased the expression of BMI1, ALDH1 and CD44 in SCCHN cell lines. Expression of NLRP3, ASC, Caspase-1, IL-1β, IL-18, BMI1, ALDH1 and CD44 was upregulated in Tgfbr1/Pten 2cKO mouse SCCHN model, and NLRP3 inflammasome expression was closely related to those CSCs makers in mice SCCHN. However, MCC950 treatment reduced the expression of NLRP3 inflammasome, CSCs markers BMI1, ALDH1 and CD44 in Tgfbr1/Pten 2cKO mice SCCHN. In addition, blockade of NLRP3 inflammasome can also delayed the tumor-burdened speed in SCCHN mice. Conclusions Our study demonstrates that NLRP3 inflammasome was upregulated and associated with the carcinogenesis and CSCs self-renewal activation in SCCHN. NLRP3 inflammasome can be a potential target in the development of novel approaches for head and neck squamous cell carcinoma therapy. |
| first_indexed | 2024-04-13T21:29:10Z |
| format | Article |
| id | doaj.art-db66c8564dc84d278a023404b5a8f8a5 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T21:29:10Z |
| publishDate | 2017-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-db66c8564dc84d278a023404b5a8f8a52022-12-22T02:29:13ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662017-09-0136111310.1186/s13046-017-0589-yNLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinomaCong-Fa Huang0Lei Chen1Yi-Cun Li2Lei Wu3Guang-Tao Yu4Wen-Feng Zhang5Zhi-Jun Sun6The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan UniversityAbstract Background NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CSCs) of squamous cell carcinoma of the head and neck (SCCHN) remain ambiguous. Methods In our study, tissue microarrays, ELISA, sphere-forming assay, colony formation assay and Western blot analysis were performed to evaluate the effect of NLRP3 inflammasome on the development of CSCs in human SCCHN tissue specimen, cell lines, and transgenic mouse SCCHN model. Results The components of NLRP3 inflammasome, namely, NLRP3, ASC, Caspase-1, and IL-18 were correlated with CSCs markers BMI1, ALDH1 and CD44 in human SCCHN specimens. Moreover, NLRP3, Caspase-1, IL-1β, and IL-18 were highly expressed in SCCHN cell lines. NLRP3 inflammasome activated by LPS and ATP promoted sphere-forming and colony formation capacities along with an upregulation of BMI1, ALDH1 and CD44. In addition, NLRP3 inflammasome blockade by NLRP3 inhibitor MCC950 reduced sphere and colony number, also decreased the expression of BMI1, ALDH1 and CD44 in SCCHN cell lines. Expression of NLRP3, ASC, Caspase-1, IL-1β, IL-18, BMI1, ALDH1 and CD44 was upregulated in Tgfbr1/Pten 2cKO mouse SCCHN model, and NLRP3 inflammasome expression was closely related to those CSCs makers in mice SCCHN. However, MCC950 treatment reduced the expression of NLRP3 inflammasome, CSCs markers BMI1, ALDH1 and CD44 in Tgfbr1/Pten 2cKO mice SCCHN. In addition, blockade of NLRP3 inflammasome can also delayed the tumor-burdened speed in SCCHN mice. Conclusions Our study demonstrates that NLRP3 inflammasome was upregulated and associated with the carcinogenesis and CSCs self-renewal activation in SCCHN. NLRP3 inflammasome can be a potential target in the development of novel approaches for head and neck squamous cell carcinoma therapy.http://link.springer.com/article/10.1186/s13046-017-0589-yNLRP3InflammasomeSCCHNCancer stem cells |
| spellingShingle | Cong-Fa Huang Lei Chen Yi-Cun Li Lei Wu Guang-Tao Yu Wen-Feng Zhang Zhi-Jun Sun NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma Journal of Experimental & Clinical Cancer Research NLRP3 Inflammasome SCCHN Cancer stem cells |
| title | NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma |
| title_full | NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma |
| title_fullStr | NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma |
| title_full_unstemmed | NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma |
| title_short | NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma |
| title_sort | nlrp3 inflammasome activation promotes inflammation induced carcinogenesis in head and neck squamous cell carcinoma |
| topic | NLRP3 Inflammasome SCCHN Cancer stem cells |
| url | http://link.springer.com/article/10.1186/s13046-017-0589-y |
| work_keys_str_mv | AT congfahuang nlrp3inflammasomeactivationpromotesinflammationinducedcarcinogenesisinheadandnecksquamouscellcarcinoma AT leichen nlrp3inflammasomeactivationpromotesinflammationinducedcarcinogenesisinheadandnecksquamouscellcarcinoma AT yicunli nlrp3inflammasomeactivationpromotesinflammationinducedcarcinogenesisinheadandnecksquamouscellcarcinoma AT leiwu nlrp3inflammasomeactivationpromotesinflammationinducedcarcinogenesisinheadandnecksquamouscellcarcinoma AT guangtaoyu nlrp3inflammasomeactivationpromotesinflammationinducedcarcinogenesisinheadandnecksquamouscellcarcinoma AT wenfengzhang nlrp3inflammasomeactivationpromotesinflammationinducedcarcinogenesisinheadandnecksquamouscellcarcinoma AT zhijunsun nlrp3inflammasomeactivationpromotesinflammationinducedcarcinogenesisinheadandnecksquamouscellcarcinoma |