Abstract
Cancer progression is linked to physical properties, cellular and biochemical composition of the tissue environment including the extracellular matrix (ECM). The ECM not only provides signaling cues by presenting ligands, but also plays a key role in mechano-sensing: modulation of biochemical pathways by physical forces. Collagens are one of the most abundant components of the ECM. We previously reported that head and neck squamous cell carcinoma (HNSCC), which is the 6th most common cause of cancer mortality worldwide with < 40% 5-year survival rates, express higher levels of collagen 11a1 (Col11a1) than normal adjacent mucosa. Col11a1 is a minor fibrillar collagen whose main physiologic role is to regulate the diameter of major collagen fibrils in the cartilage. Although reported that Col11a1 facilitates HNSCC proliferation and invasion, not much is known about its role in the tumor microenvironment. We tested the hypothesis that Col11a1-cancer interdependence facilitates tumor adhesion and metastatic colonization. We developed ECM substrates from cell lines and HNSCC tumor tissue that were characterized by scanning electron microscopy and immunofluorescence microscopy. Electrospun meshes with ECM substrates were developed and used to assess HNSCC adhesion, proliferation and motility. We used a 3D multi-cell type spheroid culture model called the primitive-lung-in-a-dish (PLiD) to demonstrate that Col11a1 siRNA targeting attenuates HNSCC colonization in the lung. Further, using homogenized and lyophilized decellularized ECM from mouse lungs, we demonstrate that Col11a1 regulates motility of HNSCC. Overall, we have used several models to elucidate the role of Col11a1 in HNSCC adhesion and metastatic colonization.
Citation Format: Sufi M. Thomas, Jonathan Enders, Greta Isai, Andras Czirok. ECM scaffolds to elucidate the role of Col11a1 in head and neck cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 61.