Abstract 3369: Nuclear hormone receptor profiling of skin cancer-associated fibroblasts for targeted pharmacological modulation of skin squamous cell carcinoma

Background: Cutaneous squamous cell carcinoma (SCC) is the second-most frequently diagnosed non-melanoma skin cancer that commonly manifests in sun-exposed areas of the skin, resulting in permanent disfigurement and potentially death when untreated. The development and malignant progression of skin SCC is dependent not only on the properties of the tumor epithelia but also the effects of the tumor stroma. Cancer associated fibroblasts (CAFs) are enriched in the stroma of skin SCC tumors and supply paracrine factors that encourage tumor growth. However, the transcription regulatory networks enabling this pro-tumor secretory phenotype of CAFs remain largely unknown. Nuclear receptors, being ligand-inducible transcription factors, are relevant therapeutic candidates for modulation of CAF-dependent SCC tumor advancement.Materials and methods: Laser capture microdissected CAFs from archived patient SCC biopsies were profiled for their expression of 48 known nuclear receptors. siRNA knockdown and overexpression of specific nuclear receptors in CAFs was performed, and their impact on the SCC transcriptome and phenotype was evaluated in a co-culture system. Co-administration of nuclear receptor ligands and conventional anticancer chemotherapeutics was also carried out in a 3D-organotypic skin tumor model to investigate synergistic and sensitizing effects on SCC.Findings and conclusions: Our study is the first to define a nuclear receptor profile for SCC CAFs, wherein the expression o...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Tumor Biology Source Type: research