Juliet Hemmati

Analysis of the TGF induced enhancement of procollagen I secretion

Collagen is the most abundant protein in mammals: it is essential for tissue development and homeostasis, and its dysfunction contributes to tumor progression. As a major component of the extracellular matrix (ECM), collagen is secreted by specialized cells such as fibroblasts. In the tumor microenvironment, transforming growth factor- (TGF) released by tumors can stimulate fibroblasts to produce more collagen, among many other proteins. In a recent study, when TGF was supplemented to cultured fibroblasts, transcription of procollagen I (PC1) more than doubled and so did the amount incorporated into the ECM. I hypothesize that, in response to increased synthesis, the secretory pathway is upregulated to more efficiently transport PC1 out of the cell, where it is incorporated into the ECM. I will measure the expression level of secretory proteins that are necessary for PC1 secretion by immunoblotting, and elevated expression would be consistent with my hypothesis. In a parallel experiment, I will study by immunofluorescence microscopy whether secretory organelles are enlarged to accommodate the increased production of secretory cargos. Together, I aim to examine the mechanisms involved in enhancement of collagen deposition by TGF. This will help us better understand the role of collagen secretion within the tumor microenvironment.