Carboxymethylcellulose hydrogels support cns-derived tumor cell chemotactic migration

Abstract

The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix (ECM) and the cell-ECM relationship. ECM is a complex network of molecules with distinct mechanical and biochemical characteristics. When the mechanisms that are in place to maintain ECM homeostasis are deregulated, most likely, this is the onset of cancer. The ECM becomes highly disorganized and the cell-matrix relationship changes, thus promoting alternations in cell mechanisms and metastasis. Medulloblastoma (MB) is one of the most common, malignant pediatric brain tumors in the United States. In order to gain a better understanding between the cell-ECM relationship and cell migratory responses in tumors we investigate 7 different types of ECM proteins via a MB-derived cell line: Poly-D-Lysine (PDL), Matrigel, Laminin, Collagen-1, Fibronectin, a 10% blend of Laminin-Collagen1, a 20% blend of Laminin-Collagen 1 and a new cellulose derived hydrogel, carboxymethylcellulose (CMC). Over time, the average changes in cell morphology, in 2D and 3D, are quantified. Data reveals CMC allows for a cell-ECM relationship typically believed to present in tumors, with cell exhibiting amoeboidal morphology that is believed to indicate the ready-ness of a cell to migrate within a given environment. Further investigation into the CMC hydrogels reveal a polysaccharide that allows for chemotactic study of MB-derived Daoy cells enabling minimal haptotactic migration conducive in the mechanistic study of the cells’ chemotactic behavior. Understanding the cell-ECM relationship provides insight into their interactions and the information obtained can be utilized in studying the natural migratory patterns of cells. CMC allows for such a behavior to be studied along with testing the motility of Daoy cells because the hydrogel provides minimal integrin interaction between the cells and the ECM. This study provides insights into understanding the mechanisms behind tumor-associated migratory patterns via chemokines. The data reflects a new possibility of tackling central nervous system (CNS) diseases by utilizing a platform of natural hydrogels to generate therapies inhibiting metastasis