Physical Forces in Glioblastoma Migration: A Systematic Review

Abstract

The invasive capabilities of glioblastoma (GBM) define the cancer’s aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences the molecular behavior of cells, both epigenetically and genetically. Current forces being studied include properties of the extracellular matrix (ECM), such as stiffness and “sensing” capabilities. There is currently limited data on the physical forces in GBM—both relating to how they influence their environment and how their environment influences them. This review outlines the advances that have been made in the field. It is our hope that further investigation of the physical forces involved in GBM will highlight new therapeutic options and increase patient survival. A search of the PubMed database was conducted through to 23 March 2022 with the following search terms: (glioblastoma) AND (physical forces OR pressure OR shear forces OR compression OR tension OR torsion) AND (migration OR invasion). Our review yielded 11 external/applied/mechanical forces and 2 tumor microenvironment (TME) forces that affect the ability of GBM to locally migrate and invade. Both external forces and forces within the tumor microenvironment have been implicated in GBM migration, invasion, and treatment resistance. We endorse further research in this area to target the physical forces affecting the migration and invasion of GBM.

A bioinformatics analysis: ZFHX4 is associated with metastasis and poor survival in ovarian cancer

“…In turn, ECM remodeling could be conducive to cancer metastasis [19]. In the primary sites, basement membranes, which lined the basal surface of tumors and presented as dense collagen structures, were broken through proteolytic ECM degradation and non-proteolytic force by neoplastic cells and cancer-associated fibroblasts (CAFs) when tumor rapid growth led to diffusion-limited oxygen and nutrient supply [20][21][22]. Next, collagens in interstitial matrix were linearized by tumor-derived lysyl oxidase (LOX), which created migratory tracks used for the migration of the tumor cells [23,24].…”

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“…GBM can release cell signaling molecules to influence the TME by promoting tumor angiogenesis and inducing immune tolerance, while immune cells within the TME influence GBM cell growth and development ( 25 ). Furthermore, the non-tumor elements of the TME have a clear role in promoting GBM cell proliferation and invasion ( 26 ). The presence of the GBM TME enhances the capacity for GBM cell proliferation, migration and immune escape, thereby promoting the development of GBM.…”

Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments

“…Further evidence has also linked CSV to tumour growth, evidenced by its upregulation in various cancer types ranging from oral cancer, breast cancer, colon cancer, prostate cancer etc [53][54][55][56][57]. The presence of CSV in brain cancer and model cell lines has also been shown for numerous tumours in the CNS; however, the amounts of CSV are highly dependent on cell type, patient, and also treatment regimens [58][59][60][61]. While CSV is often upregulated in GBM, it has also been shown to be expressed at high levels in the brain endothelium cells, suggesting that these ligands could help in both BBB crossing and specifically targeting GBM cells [61][62][63][64].…”