Carboxymethylcellulose hydrogels support central nervous system-derived tumor-cell chemotactic migration: comparison with conventional extracellular matrix macromolecules.
The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix and the cell-extracellular matrix relationship. The extracellular matrix is a complex network of macromolecules with distinct mechanical and biochemical characteristics. Disruptions in extracellular matrix homeostasis are associated with the onset of cancer. The extracellular matrix becomes highly disorganized, and the cell-matrix relationship changes, resulting in altered cell-signaling processes and metastasis. Medulloblastoma is one of the most common malignant pediatric brain tumors in the United States. In order to gain a better understanding of the interplay between cell-extracellular matrix interactions and cell-migratory responses in tumors, eight different matrix macromolecule formulations were investigated using a medulloblastoma-derived cell line: poly-D-lysine, matrigel, laminin, collagen 1, fibronectin, a 10% blend of laminin-collagen 1, a 20% blend of laminin-collagen 1, and a cellulose-derived hydrogel, carboxymethylcellulose. Over time, the average changes in cell morphology were quantified in 2D and 3D, as was migration in the presence and absence of the chemoattractant, epidermal growth factor. Data revealed that carboxymethylcellulose allowed for a cell-extracellular matrix relationship typically believed to be present in tumors, with cells exhibiting a rounded, amoeboid morphology consistent with chemotactic migration, while the other matrices promoted an elongated cell shape as well as both haptotactic and chemotactic motile processes. Therefore, carboxymethylcellulose hydrogels may serve as effective platforms for investigating central nervous system-derived tumor-cell migration in response to soluble factors.
Department of Biomedical Engineering, The City College of New York-CUNY, USA.
Tanya
T
Singh
Department of Chemical and Biomedical Engineering, Cleveland State University, USA.
Chandrasekhar
C
Kothapalli
Department of Biomedical Engineering, The City College of New York-CUNY, USA.
Devika
D
Varma
Department of Biomedical Engineering, The City College of New York-CUNY, USA.
Steven B
SB
Nicoll
Department of Biomedical Engineering, The City College of New York-CUNY, USA vazquez@me.ccny.cuny.edu.
Maribel
M
Vazquez
D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D045744:Cell Line, Tumor; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000473:pathology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D009362:Neoplasm Metastasis
D020100:Hydrogels; D002266:Carboxymethylcellulose Sodium
Medulloblastoma; carboxymethylcellulose; chemotaxis; macromolecules; migration