scholarly journals Cathepsins B, D, and G Are Expressed in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Felix Humphries ◽  
Bridget Chang-McDonald ◽  
Josie Patel ◽  
Nicholas Bockett ◽  
Erin Paterson ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Enzyme Activity ◽  
Mast Cells ◽  
Cell Carcinoma ◽  
Cathepsin B ◽  
Immunohistochemical Staining ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Cathepsin G ◽  
Transcript Expression ◽  
Tissue Samples

AimWe have previously demonstrated the presence of two cancer stem cell (CSC) subpopulations within metastatic head and neck cutaneous squamous cell carcinoma (mHNcSCC) expressing components of the renin-angiotensin system (RAS), which promotes tumorigenesis. Cathepsins B, D and G are enzymes that constitute bypass loops for the RAS. This study investigated the expression and localization of cathepsins B, D, and G in relation to CSC subpopulations within mHNcSCC.MethodsImmunohistochemical staining was performed on mHNcSCC tissue samples from 20 patients to determine the expression and localization of cathepsins B, D, and G. Immunofluorescence staining was performed on two of these mHNcSCC tissue samples by co-staining of cathepsins B and D with OCT4 and SOX2, and cathepsin G with mast cell markers tryptase and chymase. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were performed on five mHNcSCC samples and four mHNcSCC-derived primary cell lines, to determine protein and transcript expression of these three cathepsins, respectively. Enzyme activity assays were performed on mHNcSCC tissue samples to determine whether these cathepsins were active.ResultsImmunohistochemical staining demonstrated the presence of cathepsins B, D and G in in all 20 mHNcSCC tissue samples. Immunofluorescence staining showed that cathepsins B and D were localized to the CSCs both within the tumor nests and peri-tumoral stroma (PTS) and cathepsin G was localized to the phenotypic mast cells within the PTS. Western blotting demonstrated protein expression of cathepsin B and D, and RT-qPCR demonstrated transcript expression of all three cathepsins. Enzyme activity assays showed that cathepsin B and D to be active.ConclusionThe presence of cathepsins B and D on the CSCs and cathepsin G on the phenotypic mast cells suggest the presence of bypass loops for the RAS which may be a potential novel therapeutic target for mHNcSCC.

scholarly journals Investigation of effect of vitamin D receptor, calcium-sensing receptor and β-catenin on cutaneous squamous cell carcinoma

2020 ◽  
Vol 45 (1) ◽  
pp. 91-98
Author(s):  
Berrin Tuğrul ◽  
Sevinç Söylev ◽  
Peyker Temiz ◽  
Gülsüm Gençoğlan
Keyword(s):  
Vitamin D ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Vitamin D Receptor ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Beta Catenin ◽  
Calcium Sensing Receptor ◽  
Tissue Samples ◽  
Calcium Sensing

AbstractBackgroundCutaneous squamous cell carcinoma (cSCC) is a malignant and invasive tumor which is originated from epidermis with a high incidence among non-melanoma skin cancers. The aim of this study was to determine whether vitamin D receptor (VDR), calcium-sensing receptor (CaSR) and beta catenin (β-catenin) proteins have an effect on cSCC.Materials and methodsVDR, CaSR and β-catenin proteins in tissue samples of cSCC and control group were analyzed by immunohistochemistry (IHC) and Western blotting (WB) method. IHC findings were statistically evaluated.ResultsIHC staining density of VDR and β-catenin were higher in cSCC tissue samples than control. The difference between IHC staining density of VDR and β-catenin in the patient and the control groups were statistically significant (p = 0.021, p = 0.021, respectively), but not for CaSR (p = 0.237). While the VDR and β-catenin staining rates obtained by the IHC method could be supported by WB results, the WB bands for CaSR could not be shown.ConclusionThe findings suggest that VDR and β-catenin may have an effect on the disease. Further research is required to better understand the role of VDR and β-catenin together on cSCC.

scholarly journals Cancer Stem Cells in Metastatic Head and Neck Cutaneous Squamous Cell Carcinoma Express Components of the Renin-Angiotensin System

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 243
Author(s):  
Sam Siljee ◽  
Olivia Buchanan ◽  
Helen D. Brasch ◽  
Nicholas Bockett ◽  
Josie Patel ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Angiotensin Ii ◽  
Cell Lines ◽  
Immunohistochemical Staining ◽  
Renin Angiotensin System ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Angiotensin Ii Receptor ◽  
Tissue Samples ◽  
Angiotensin System ◽  
Primary Cell Lines

We investigated the expression of components of the renin-angiotensin system (RAS) by cancer stem cell (CSC) subpopulations in metastatic head and neck cutaneous squamous cell carcinoma (mHNcSCC). Immunohistochemical staining demonstrated expression of prorenin receptor (PRR), angiotensin-converting enzyme (ACE), and angiotensin II receptor 2 (AT2R) in all cases and angiotensinogen in 14 cases; however, renin and ACE2 were not detected in any of the 20 mHNcSCC tissue samples. Western blotting showed protein expression of angiotensinogen in all six mHNcSCC tissue samples, but in none of the four mHNcSCC-derived primary cell lines, while PRR was detected in the four cell lines only. RT-qPCR confirmed transcripts of angiotensinogen, PRR, ACE, and angiotensin II receptor 1 (AT1R), but not renin or AT2R in all four mHNcSCC tissue samples and all four mHNcSCC-derived primary cell lines, while ACE2 was expressed in the tissue samples only. Double immunohistochemical staining on two of the mHNcSCC tissue samples showed expression of angiotensinogen by the SOX2+ CSCs within the tumor nests (TNs), and immunofluorescence showed expression of PRR and AT2R by the SOX2+ CSCs within the TNs and the peritumoral stroma (PTS). ACE was expressed on the endothelium of the tumor microvessels within the PTS. We demonstrated expression of angiotensinogen by CSCs within the TNs, PRR, and AT2R by the CSCs within the TNs and the PTS, in addition to ACE on the endothelium of tumor microvessels in mHNcSCC.

Cutaneous squamous cell carcinoma progression is associated with decreased GATA-3 immunohistochemical staining

2016 ◽  
Vol 43 (4) ◽  
pp. 347-353 ◽  
Author(s):  
Jason F. Solus ◽  
Khaled Hassan ◽  
Sena J. Lee ◽  
Andy C. Hsi ◽  
Ilana S. Rosman ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Immunohistochemical Staining ◽  
Cutaneous Squamous Cell Carcinoma

scholarly journals Expression of Cathepsins B, D, and G in Extracranial Arterio-Venous Malformation

2021 ◽  
Vol 8 ◽  
Author(s):  
Lauren Hansen ◽  
Helen D. Brasch ◽  
Erin Paterson ◽  
Josie Patel ◽  
Nicholas Bockett ◽  
...  
Keyword(s):  
Mast Cells ◽  
Enzymatic Activity ◽  
Cell Lines ◽  
Immunohistochemical Staining ◽  
Venous Malformation ◽  
Primary Cell ◽  
Cathepsin G ◽  
Tissue Samples ◽  
Primary Cell Lines ◽  
Arterio Venous Malformation

Objectives: We have previously identified a population of cells that expressed stemness-associated markers in extracranial arterio-venous malformation (AVM) and demonstrated expression of cathepsins B, D, and G on embryonic stem cell (ESC)-like populations in other vascular anomalies. This study investigated the expression of cathepsins B, D, and G, and their localization in relation to this primitive population in extracranial AVM.Methods: Immunohistochemical staining was performed on AVM tissue samples from 13 patients to demonstrate expression of cathepsins B, D, and G. Western blotting was performed on four AVM tissue samples and three AVM-derived primary cell lines to confirm protein expression of cathepsins B and D proteins. RT-qPCR was performed on three AVM-derived primary cell lines to demonstrate transcript expression of cathepsins B, D, and G. Enzymatic activity assays were performed on three AVM-derived primary cell lines to investigate if cathepsins B and D were active. Localization of the cathepsins was investigated using immunofluorescence dual-staining of the cathepsins with the ESC markers OCT4 and SOX2, and mast cells marker chymase on two of the 13 AVM tissue samples.Results: Immunohistochemical staining demonstrated expression of cathepsins B, D, and G in all 13 AVM tissue samples. Western blotting showed expression of cathepsins B and D proteins in all four AVM tissue samples and all three AVM-derived primary cell lines. RT-qPCR demonstrated transcripts of cathepsins B, D, and G in all three AVM-derived primary cell lines. Enzymatic activity assays showed that cathepsins B and D were active. Immunofluorescence staining showed expression of cathepsins B and D on the OCT4+/SOX2+ endothelium and media of the lesional vessels and cells within the stroma in AVM nidus. Cathepsin G was expressed on the chymase+ phenotypic mast cells.Conclusions: This study demonstrated the novel finding of the expression of cathepsins B, D, and G in AVM. Cathepsins B and D were expressed by the primitive population, and cathepsin G was localized to mast cells, within the AVM nidus.

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