Cancer stem cells within moderately differentiated head and neck cutaneous squamous cell carcinoma express components of the renin-angiotensin system

Nallaiah, Shanella; Lee, Valerie Ming Yi; Brasch, Helen D.; Jongh, Jennifer de; Schaijik, Bede van; Marsh, Reginald; Tan, Swee T.; Itinteang, Tinte

doi:10.1016/j.bjps.2018.11.013

Cited by 15 publications

(20 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Expression of components of the renin-angiotensin system (RAS) by CSCs has been demonstrated in different cancer types including glioblastoma ( 64 ), OCSCC affecting the oral tongue ( 65 ), buccal mucosa ( 66 ), and lip ( 67 ) squamous cell carcinoma (SCC), primary HNcSCC ( 68 ), metastatic colon adenocarcinoma ( 42 ), and metastatic malignant melanoma ( 43 ). This suggests CSCs in these tumors may be targeted by modulation of the RAS ( 12 , 55 ).…”

Section: Discussionmentioning

confidence: 99%

Cancer Stem Cell Subpopulations Are Present Within Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma

et al. 2020

Self Cite

View full text Add to dashboard Cite

Cancer stem cells (CSCs) have been identified in many cancer types including primary head and neck cutaneous squamous cell carcinoma (HNcSCC). This study aimed to identify and characterize CSCs in metastatic HNcSCC (mHNcSCC). Immunohistochemical staining performed on mHNcSCC samples from 15 patients demonstrated expression of the induced pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4, and c-MYC in all 15 samples. In situ hybridization and RT-qPCR performed on four of these mHNcSCC tissue samples confirmed transcript expression of all five iPSC markers. Immunofluorescence staining performed on three of these mHNcSCC samples demonstrated expression of c-MYC on cells within the tumor nests (TNs) and the peri-tumoral stroma (PTS) that also expressed KLF4. OCT4 was expressed on the SOX2+/NANOG+/KLF4+ cells within the TNs, and the SOX2+/NANOG+/KLF4+ cells within the PTS. RT-qPCR demonstrated transcript expression of all five iPSC markers in all three mHNcSCC-derived primary cell lines, except for SOX2 in one cell line. Western blotting showed the presence of SOX2, KLF4, and c-MYC but not OCT4 and NANOG in the three mHNcSCC-derived primary cell lines. All three cell lines formed tumorspheres, at the first passage. We demonstrated an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ CSC subpopulation and an OCT4+/NANOG-/SOX2+/KLF4+/c-MYC+ subpopulation within the TNs, and an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ subpopulation within the PTS of mHNcSCC.

show abstract

Section: Discussionmentioning

confidence: 99%

Cancer Stem Cell Subpopulations Are Present Within Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“… 48 , 49 We have recently shown the expression of the RAS components: PRR, ACE, AT 1 R, and AT 2 R by these CSC subpopulations in MDHNcSCC. 28 …”

Section: Discussionmentioning

confidence: 99%

“…MDHNcSCC tissue samples from 10 male and 5 female patients aged 42–99 years (mean, 76.3 years), including those used in the previous studies, 27 , 28 were sourced from the Gillies McIndoe Research Institute Tissue Bank for this study. The Central Regional Health and Disability Ethics Committee approved this study (Ref.…”

Section: Methodsmentioning

confidence: 99%

“…The protein was separated by SDS-PAGE and transferred to a PVDF membrane. 28 Detection of protein was performed on the iBind Flex (cat.#SLF200; Thermo Fisher Scientific) using the primary antibodies for cathepsin B (1:250; cat.#sc-6490-R; Santa Cruz), cathepsin D (1:250; cat.#sc-6486; Santa Cruz), cathepsin G (1:500; cat.#ab197354; Abcam), and α-tubulin (1:1000; cat.#62204; Thermo Fisher Scientific). Secondary antibodies (all from Life Technologies) used were goat anti-rabbit Alexa Fluor 647 (1:2000; cat.#A-21244) for cathepsin B, chicken anti-goat Alexa Fluor 647 (1:2000; cat.#A-21469) for cathepsin D, donkey anti-mouse Alexa Fluor 488 (1:2000; cat.#A-21202) for α-tubulin, and goat anti-rabbit horseradish peroxidase (HRP) (1:2000; cat.#ab6721; Abcam) for the detection of cathepsin G in the cell lines.…”

Section: Methodsmentioning

confidence: 99%

“… 27 These primitive cells express components of the RAS: prorenin receptor (PRR), angiotensin-converting enzyme (ACE), angiotensin receptor 1 (AT 1 R), and angiotensin receptor 2 (AT 2 R). 28 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cancer Stem Cells in Head and Neck Cutaneous Squamous Cell Carcinoma Express Cathepsins

Featherston

Brasch

Siljee

et al. 2020

Plastic and Reconstructive Surgery - Global Open

Self Cite

View full text Add to dashboard Cite

Background: Cancer stem cell (CSC) subpopulations within moderately differentiated head and neck cutaneous squamous cell carcinoma (MDHNcSCC) express the components of the renin–angiotensin system (RAS). This study investigated the expression of cathepsins B, D, and G, which constitute bypass loops of the RAS, by CSCs in MDHNcSCC. Methods: Immunohistochemical staining was performed on MDHNcSCC tissue samples from 15 patients to determine the expression of cathepsins B, D, and G. Co-localization of these cathepsins with the embryonic stem cell markers Octamer-binding transcription factor 4 (OCT4) and c-MYC was investigated with immunofluorescence staining. Reverse transcription quantitative polymerase chain reaction was performed on 5 MDHNcSCC tissue samples to investigate transcript expression of cathepsins B, D and G. Western blotting and enzymatic activity assays were performed on 5 MDHNcSCC tissue samples and 6 MDHNcSCC-derived primary cell lines to confirm protein expression, transcript expression, and functional activity of these cathepsins, respectively. Results: Immunohistochemical staining demonstrated the expression of cathepsins B, D, and G in all MDHNcSCC tissue samples. Immunofluorescence staining showed localization of cathepsins B and D to the c-MYC+ CSC subpopulations and the OCT4+ CSC subpopulations within the tumor nests and the peritumoral stroma. Cathepsin G was expressed on the tryptase+/c-MYC+ cells within the peritumoral stroma. Reverse transcription quantitative polymerase chain reaction demonstrated transcript expression of cathepsins B, D and G in the MDHNcSCC tissue samples. Western blotting and enzymatic activity assays confirmed protein expression and functional activity of cathepsins B and D in the MDHNcSCC tissue samples and MDHNcSCC-derived primary cell lines, respectively. Conclusions: Cathepsins B, D, and G are expressed in MDHNcSCC with functionally active cathepsins B and D localizing to the CSC subpopulations, and cathepsin G is expressed by mast cells, suggesting the potential use of cathepsin inhibitors in addition to RAS blockade to target CSCs in MDHNcSCC.

show abstract

Cancer Stem Cells in the Head and Neck Cancers

Kilmister

Tan

2022

Atlas of Extreme Facial Cancer

View full text Add to dashboard Cite

Cancer stem cells within moderately differentiated head and neck cutaneous squamous cell carcinoma express components of the renin-angiotensin system

Cited by 15 publications

References 32 publications

Cancer Stem Cell Subpopulations Are Present Within Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma

Cancer Stem Cell Subpopulations Are Present Within Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma

Cancer Stem Cells in Head and Neck Cutaneous Squamous Cell Carcinoma Express Cathepsins

Cancer Stem Cells in the Head and Neck Cancers

Contact Info

Product

Resources

About