Influence of solid-phase growth factor presentation on triple-negative breast cancer cells
Heparin (HP) and Hyaluronic acid (HA)-based hydrogels have long been used for 3D culture of cancer cells. Our lab worked on studying how interactions of growth factors (specifically EGF) with binding moieties such as HP and HA in the microenvironment can alter the morphology and phenotype of breast cancer cells. Our paper is now published in Biomaterials Science. Below is a brief description of the study.
Heparin-based hydrogel scaffolding alters the transcriptomic profile and increases the chemoresistance of MDA-MB-231 triple-negative breast cancer cells
The tumor microenvironment plays a critical role in the proliferation and chemoresistance of cancer cells. Growth factors (GFs) are known to interact with the extracellular matrix (ECM) via heparin binding sites, and these associations influence cell behavior. In the present study, we demonstrate the ability to define signals presented by the scaffold by pre-mixing growth factors, such as epidermal growth factor, into the heparin-based (HP-B) hydrogel prior to gelation. In the 3D biomimetic microenvironment, breast cancer cells formed spheroids within 24 hours of initial seeding. Despite higher number of proliferating cells in 2D cultures, 3D spheroids exhibited a higher degree of chemoresistance after 72 hours. Further, our RNA sequencing results highlighted the phenotypic changes influenced by solid-phase GF presentation. Wnt/β-catenin and TGF-β signaling were upregulated in the cells grown in the hydrogel, while apoptosis, IL2-STAT5 and PI3K-AKT-mTOR signaling were downregulated. With emerging technologies for precision medicine in cancer, this nature of fine-tuning the microenvironment is paramount for cultivation and downstream characterization of primary cancer cells and rare circulating tumor cells (CTCs), and effective screening of chemotherapeutic agents.
Ongoing Studies of the Tumor Microenvironment
Current studies in the lab are focused on developing PDMS-based microfluidic platforms to incorporate our biomimetic hydrogel microenvironment, to study the immune cell behavior, specifically neutrophil migration and NETosis in the absence/presence of certain environmental cues.