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AACR 2022: Correlation of Cell Proliferation and Retinoid Response in Squamous Cell Skin Cancer

By: Vanessa A. Carter, BS
Posted: Wednesday, April 27, 2022

Cells permanently exit the cell cycle after undergoing terminal differentiation and adopting their tissue-specific functions, making differentiation a notable target for cancer prevention and treatment. These were the findings of Ivan Litvinov, MD, PhD, of McGill University, Montreal, and colleague. Preferentially expressed antigen in melanoma (PRAME) expression in squamous cell carcinoma was thought to be related to resistance to antineoplastic effects of retinoids, in turn supporting cell proliferation. These findings were presented during the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 5734).

“We conclude that PRAME enhances proliferation of malignant keratinocytes in vitro and may confer resistance to retinoid-induced differentiation and proliferation arrest,” mentioned the study authors. “Investigations to assess the prognostic and therapeutic significance of PRAME expression in squamous cell carcinomas are warranted.”

Immunoblotting and quantitative real-time polymerase chain reaction were used to evaluate PRAME expression in human cutaneous squamous cell carcinoma tumors and cell lines, as well as head and neck squamous cell carcinoma cell lines. PRAME-overexpressing immortalized keratinocyte, cutaneous squamous cell carcinoma, and head and neck squamous cell carcinoma cell lines were generated. Additionally, short hairpin RNA–mediated knockdown of PRAME was performed in each cell line.

Cells were treated with all-trans retinoic acid (ATRA) for 24, 48, or 72 hours. Quantitative real-time polymerase chain reaction and immunoblotting were used to assess the expression of differentiation markers. Immunoblot analysis of cell-cycle genes, cell counting assays, and Ki67 immunofluorescence staining were carried out to examine proliferation.

Expression of PRAME was detected in subsets of cutaneous squamous cell carcinoma tumors and various squamous cell carcinoma cell lines. Compared with control cells, cell proliferation in head and neck squamous cell carcinoma cells appeared to be enhanced upon PRAME overexpression; treatment with ATRA did not promote differentiation. Of note, the antiproliferative effect of ATRA was decreased upon PRAME overexpression in these cells.

Disclosure: The study authors reported no conflicts of interest.


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