Radiation-induced motility alterations in medulloblastoma cells

Abstract

Photon irradiation has been repeatedly suspected of increasing tumor cell motility and promoting locoregional recurrence of disease. This study was set up to analyse possible mechanisms underlying the potentially radiation-altered motility in medulloblastoma cells. Medulloblastoma cell lines D425 and Med8A were analyzed in migration and adhesion experiments with and without photon and carbon ion irradiation. Expression of integrins was determined by quantitative FACS analysis. Matrix metalloproteinase concentrations within cell culture supernatants were investigated by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Student's t-test. Both photon and carbon ion irradiation significantly reduced chemotactic medulloblastoma cell transmigration through 8-μm pore size membranes, while simultaneously increasing adherence to fibronectin- and collagen I- and IV–coated surfaces. Correspondingly, both photon and carbon ion irradiation downregulate soluble MMP9 concentrations, while upregulating cell surface expression of proadhesive extracellular matrix protein-binding integrin α5. The observed phenotype of radiation-altered motility is more pronounced following carbon ion than photon irradiation. Both photon and (even more so) carbon ion irradiation are effective in inhibiting medulloblastoma cell migration through downregulation of matrix metalloproteinase 9 and upregulation of proadhesive cell surface integrin α5, which lead to increased cell adherence to extracellular matrix proteins.

Combined EphB2 receptor knockdown with radiation decreases cell viability and invasion in medulloblastoma

“…Our findings show that when DAOY and UW228 cells were exposed to radiation, it resulted in decreased cell invasion. This is consistent with the findings published by Rieken et al [10]. The key observation in our experiments is the significant reduction in invasive potential of medulloblastoma cells following combined inhibition of EphB2 knockdown with radiation compared to other groups.…”

“…In contrast to some observations in medulloblastoma cells [9, 11] and in non-medulloblastoma tumor cells [12], our data show that ionizing radiation did not promote tumor cell invasion but instead significantly decreased invasion, particularly in combination with EphB2 knockdown, which is consistent with other reports [10]. In addition, we found that knockdown of EphB2, combined with radiation, decreased cell viability and clonogenic survival, in part through the inhibition of cell cycle progression.…”

“…Photon irradiation (IR), a standard of care in medulloblastoma treatment, has been suggested to enhance medulloblastoma cell invasion, and preclinical studies have demonstrated increased tumor cell invasiveness through upregulation of urokinase plasminogen activator receptor (uPAR) signaling [9]. Conversely, other groups have shown a decrease in migration and invasion following various dosing of photons and carbon ion irradiation [10], suggesting that additional studies are needed.…”

Carbon ion irradiation withstands cancer stem cells' migration/invasion process in Head and Neck Squamous Cell Carcinoma (HNSCC)

“…In a medulloblastoma cell line, Rieken S el al. have recently demonstrated that heavy-ions could inhibit cell migration through downregulation of MMP-9 and upregulation of proadhesive cell surface integrin alpha-5 leading to increased cell adherence to extracellular matrix proteins [56]. Carbon ion is also known to reduce levels of GTP-bound Rac1 and RhoA, two important regulators of cell motility [57].…”

EGF as a New Therapeutic Target for Medulloblastoma Metastasis

“…Further, clinical studies have illustrated that the spread of MB cells occurs predominantly to the spinal column via a combination of two-dimensional (2D) and three-dimensional (3D) movements (6, 51, 67, 77, 83) . Such spreading results from tumor cells that drop into the cerebrospinal fluid and tend to seed in parts of the spine (53, 74, 77, 79, 84) . As a result, the movement of MB cells on the surface of the spinal column can be examined on 2D substrata to plausibly physiologically approximate the metastatic behavior of these pediatric brain tumors.…”