The Role of NFAT Signaling in Fibroblast Activation: Effects on Fibroblast Invasion and Angiogenesis

Students

2020
College

Faculty

Associate Professor Of Cancer Biology
Medicine

Project Summary

An abundance of literature suggests that fibroblasts act as key players in promoting cancer by participating in the essentially every stage of disease progression; cancer-associated fibroblasts (CAFs) act as positive regulators of cancer progression, including metastasis, by creating a tumor metabolic ecosystem through symbiosis with cancer cells. By releasing growth-promoting factors and reorganizing extracellular matrix (ECM) structure through matrix metalloproteases (MMPs), it is likely that CAFs promote cancer growth and metastasis as cancer cells derive growth, migratory, and survival properties. Despite being among the most studied cell-type in biology, it is surprising to see that the fibroblast and its interaction with the ECM remain mostly enigmatic and not well understood.

My project’s goal was to observe the phenotypical differences between wildtype fibroblasts and fibroblasts that lack in CN/NFAT signaling, a cellular pathway that plays an important role in proliferation, survival, and migration. More specifically, my project consisted of 1. Establishing an optimized invasion assay of fibroblasts through a collagen matrix to assess fibroblast motility and 2. Co-culturing Fibroblasts and endothelial cells then extracting the conditioned media to assess different phenotypical expression.

Throughout the ten weeks in which I conduced my research project, I was able to establish a fibroblast invasion assay that allows fibroblast motility to be assessed in a setting that mimics the extracellular matrix and provide more information on into how fibroblasts interact with endothelial cells through soluble factors to affect the tumor microenvironment. More importantly, my research experience provided me greater insight to how different cell types such as fibroblasts and endothelial cells act as positive or negative regulators of the growth, survival, and invasion of cancer cells.

By participating in the Penn Undergraduate Mentoring Program this summer, I have gained a valuable experience in which I was able to grasp a deeper understanding in scientific research. Although my experiments in many cases were far from successful, I was able to hone my techniques through learning from my failures and continuously optimizing my protocol. With the constant help of many people from my lab, I am thankful to have been able to be part of the strive for understanding and possibly help provide greater insight in a disease that haunts the lives of many families in the world today.

The Role of NFAT Signaling in Fibroblast Activation: Effects on Fibroblast Invasion and Angiogenesis