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. 2020 Aug;140(8):1665-1669.e5.
doi: 10.1016/j.jid.2019.12.028. Epub 2020 Jan 23.

Phenotypic Plasticity of Cutaneous Squamous Cell Carcinoma Mediated by Cyclooxygenase-2

Hyeongsun Moon  1 , Dahihm Kim  2 , Leanne R Donahue  2 , Andrew C White  3
Affiliations

Phenotypic Plasticity of Cutaneous Squamous Cell Carcinoma Mediated by Cyclooxygenase-2

Hyeongsun Moon et al. J Invest Dermatol. 2020 Aug.
No abstract available

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Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.. Cox-2 is required for efficient tumor formation.
(a) Gene set enrichment analysis shows the correlation between KrasG12D and EMT markers. Original transcriptomics data were derived from the research of White et al. (2014). (b) Ptgs2 gene expression was compared between the normal mouse skin and cSCCs collected from Krt15-CrePR; LSLKrasG12D; p53flox/flox mice. n = 3/each. Error bar, SEM. (c) Experimental scheme. Krt15-CrePR; LSLKrasG12D; p53flox/flox; RosaLSLTdTomato mice were bred to animals harboring Ptgs2flox/flox genetic alleles. (d) Animal genotypes were confirmed by PCR, and (e) Cox-2 expression at the protein level in tumors originating from animals with or without Ptgs2 conditional knockout was confirmed by using western blots. (f) The Kaplan–Meier curve demonstrates a significantly longer tumor-free survival period in Ptgs2 conditional knockout animals. n = 18/group. Statistical significance: *P < 0.01, **P < 0.001. Bar = 100 μm. bp, base pairs; cSCC, cutaneous SCC; Cox-2, cyclooxygenase 2; EMT, epithelial–mesenchymal transition; fl, flox; NES, normalized enrichment score; wt, wild-type.
Figure 2.
Figure 2.. Cox-2 expression correlates with aggressive cSCC phenotypes.
(a, b) Macroscopic phenotypes of oncogenic Ras/p53-mediated cutaneous tumors originating from murine skin with or without the conditional knockout of Ptgs2. (c, d) Histological differences between cutaneous tumors with or without Cox-2 expression. TdTomato expression represents lineage tracing. (e) The histological phenotypic differences between cutaneous tumors ± Cox-2 expression. n = 15 for wild-type Cox-2 and 11 for Cox-2 knockout. (f, g) The expression pattern of cSCC (Krt14), mesenchymal (Vim), epithelial (E-Cad), and stromal fibroblast (Pdgfr-α) markers in cutaneous tumors. (h) The phenotype of primary cells isolated from cutaneous tumors were observed 16 hours after culture in vitro. (i) Relative expression levels of epithelial (E-Cad) and mesenchymal (N-Cad and Vim) markers, and Cox-2 of primary cells was examined by immunoblots. Loading control: α-tubulin. (j) Summary. Oncogenic Ras/p53-mediated cSCCs originating from Krt15+ hair follicle stem cells can be more mesenchymal-like upon the expression of cell-type specific expression of Cox-2. Bar = 100 μm. cSCC, cutaneous SCC; Cox-2, cyclooxygenase 2; fl, flox; SCC, squamous cell carcinoma; wt, wild-type.
See this image and copyright information in PMC

References

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