The effect of ALA-PDT on reversing the activation of cancer-associated fibroblasts in cutaneous squamous cell carcinoma.

Abstract

Cancer-associated fibroblasts (CAFs) are important components of the tumor microenvironment, affecting the biological behavior of tumor cells and playing critical roles in tumor growth, invasion, and metastasis. Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is an established approach for the treatment of non-melanoma skin cancers. It is reported that ALA-PDT treating cutaneous squamous cell carcinoma(cSCC) also induce antitumor immune effect and has an impact on tumor microenvironment. However, the effect of ALA-PDT on CAFs is not well known. In this study, the data showed that the expression of α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP), as well as migratory ability, were elevated in 3T3 fibroblasts co-cultured with tumor cells. Western blot, qRT-PCR and transwell cell migration assay were performed to detect these findings. In vivo, the rate of tumor growth in mice injected with a mixture of tumor cells and 3T3 fibroblasts was higher than that in mice injected with tumor cells only. Furthermore, both in co-cultured 3T3 fibroblasts and CAFs, a reduction in the expression of a-SMA and FAP was observed after ALA-PDT. Same with migratory ability. The findings indicated an inhibitory effect of ALA-PDT on the activation of CAFs in cSCC.