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Molecular Role of Cox-2 in Cutaneous Squamous Cell Carcinoma

By: Lauren Harrison, MS
Posted: Tuesday, March 24, 2020

Cyclooxygenase-2 (Cox-2) may play a key role in the formation of advanced squamous cell carcinomas, although inhibition of Cox-2 may not have the ability to fully reverse the oncogenic potential of hair follicle stem cells. Hyeongsun Moon, DVM, MS, PhD, of the University of California, Davis, and colleagues, published their research findings on phenotypic plasticity of this type of skin cancer in in a Letter to Editor in the Journal of Investigative Dermatology.

“These data indicate that primary cutaneous squamous cell carcinoma cell lines do not exhibit a full mesenchymal-to-epithelial transition when Cox-2 is suppressed in vitro, but future experiments will be needed to further explore this finding,” concluded the authors.

Researchers used mouse models to create animals with cutaneous tumors originating from hair follicle stem cells with both depletion of Cox-2 and wild-type Cox-2. Tumors that developed in the Cox-2 knockout mice grew more slowly and developed a rougher surface than tumors in the Cox-2-wild-type mice. On histologic evaluation of the Cox-2 knockout tumors, they were frequently well differentiated, with significant hyperkeratosis or papillomatous growths.

Tumors with wild-type Cox-2 expressed high levels of vimentin (a type III intermediate filament protein expressed in mesenchymal cells), low or absent levels of the cell-cell adhesion molecule E-cadherin, and a lack of clear borders between stromal fibroblasts and tumor cells. In comparison, the tumors with Cox-2 knockout had an absence of vimentin, high levels of E-cadherin, and distinct borders between the tumor cell compartments–highlighting the importance of Cox-2 in the epithelial-to-mesenchymal transition.

In addition, the authors treated primary cutaneous squamous cell carcinoma cell lines with the Cox-2 inhibitor celecoxib; it resulted in a small and transient increase in E-cadherin, but no changes in N-cadherin were observed. Cells treated with celecoxib showed a change in morphology from elongated spindle-shaped cells to large and often multinucleated cells, suggesting induction of cellular senescence.

Disclosure: The authors reported no conflicts of interest.



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