Nanofibrous Matrices Modulating Glioma Cell Migration and Proliferation and the Exploration of Their Molecular Mechanism

Abstract

The highly invasive behavior of glioma cells causes poor prognosis and high mortality. Interactions between tumor cells and the extracellular matrix (ECM) drive this invasion. Collagen produced by glioblastoma is incorporated into the tumor matrix and tends to form fibrous scaffolds that modulate tumor cell migration. However, how the fibrous topography alters these behaviors remains poorly understood. We fabricated electrospun collagen-polycaprolactone (CO/PCL) and hyaluronic acid-polycaprolactone (HA/PCL) nanofiber matrices to mimic the tumor microenvironment. Biocompatibility assays showed that primary and U87 glioma cells maintain high cell viability on these matrices. Flow cytometry revealed significantly higher cell proliferation on both nanofiber matrices compared to flat-coated substrates. Conversely, time-lapse imaging demonstrated that the fibrous structures reduced cell motility compared to flat coatings, although aligned fibers actively guided cell movement direction. These results functionally demonstrated migration−proliferation dichotomy, where the architectural cues of the fiber matrix shift tumor cells from a migratory phenotype to a proliferative state. Transcriptomic analysis via RNA-seq revealed that this behavioral shift is systematically associated with the regulation of focal adhesion and cell cycle pathways. On nanofibers, critical cell migration genes including matrix proteins (LAMA2, LAMA4, FN1, and COL6A1), membrane receptors (ITGA10 and ITGA11), and signaling molecules (RACK2 and PIP5K1C) were significantly downregulated, while cell cycle genes were upregulated. The study demonstrates the regulation of glioma biological processes by nanofibrous matrices and the relevant molecular signaling pathways.