The effect of N‐acetyl cysteine on myofibroblast phenotype expression by immortalized keratinocytes, Ker‐CT‐Ras (731.5)

Recent research activity has focused on the tumor stroma. Tumor stroma are typically connective tissues containing fibroblasts and myofibroblasts. These cells are required for the wound healing processes of the body. There is evidence that myofibroblast presence in tumor stroma leads to poor prognosis. Mechanical tension, one of three key factors, enhances differentiation of myofibroblasts. In vitro carcinomas can form through a pathway which involves the up‐regulation of the ras protein. Precancerous keratinocytes lead to two types of carcinomas. They take on properties of fibroblasts and metastasize, spreading into the dermis. Fibroblasts generate tension in the dermis during the wound healing process. Our experiment focuses on precancerous keratinocytes and their journey into the dermis, which we model using an in vitro stress‐relaxed collagen matrix. We set up Ker‐CT‐Ras lattices void of fibroblasts and generated contraction data. With Ker‐CT‐Ras as with fibroblasts, transforming growth factor beta (TGF‐beta) increases tension generating ability and up‐regulates production of stress fibers. N‐acetyl cysteine (NAC) in the lab was shown to block tgf‐beta signaling in fibroblasts. Here we focus on the effect of NAC on Ker‐CT‐Ras. Additional data presents the comparative tension‐generating ability of fibroblast lattices (DP‐147‐H‐Tert) and co‐culture lattices comprised of the two. Data taken from a monolayer (coverslip) model visually describes the structural properties of the myofibroblast phenotype. Overall, we found that response of Ker‐CT‐Ras to these signals is similar to that of fibroblasts. Grant Funding Source : Supported by CURE‐S‐STEM, OK‐LSAMP, and RCSA grants