The overall aim of the project was to investigate the existence and function of fibroblast growth factor signalling (FGF) in stromal fibroblasts of the mammary gland and its role in mammary gland development and cancer.
FGF signalling is an essential signalling pathway that mediates communication between cells, from the earliest developmental stages throughout life. Its proper function is crucial for organ development, homeostasis and regeneration, and its deregulation leads to pathologies, including cancer. In the mammary gland, FGF signalling had been known to play a role only in the epithelium. In this project, for the first time, Dr. Koledova reported and deciphered the role of FGF signalling in mammary fibroblasts in regulation of mammary epithelial branching morphogenesis, a process through which the functional architecture of the milk-producing organ is established.
To this end, the researchers had developed and used innovative 3D cell cultures, including co-cultures of mammary organoids with mammary fibroblasts, in combination with advanced imaging and molecular biology techniques. The results of this project, published in the prestigious journal Development (Q1: #4/86 in developmental biology, IF 5.763), challenge the dogmatic epithelium-centric view on the role of FGF signalling in mammary gland development. This work documents that FGF signalling is required for regulation of crucial fibroblast functions, too, which in turn impact on epithelial development.
Furthermore, the project has helped to elucidate the phenomenon of bi-phasic dose-response profile of FGF signalling. Using hyperstable variants of FGF2 in collaboration with the biotech company Enantis, Dr. Koledova uncovered new mechanisms, which regulate cellular outcomes of FGF signalling. These results were published in the journal Frontiers in Cell and Developmental Biology (Q1: #46/264 in cell biology, IF 5.206).