Biology subjects

Munson, J. M.

Publications and source records attributed to Munson, J. M..

2 recordsLinked to original sources

bioRxiv2018

Convective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine model

Glioblastoma is the most common and malignant form of brain cancer. Its invasive nature limits treatment efficacy and promotes inevitable recurrence. Previous in vitro studies have shown that interstitial fluid flow, a factor characteristically increased in cancer, increases glioma cell invasion via CXCR4-CXCL12. It is currently unknown if these effects translate in vivo. Using the therapeutic technique of convection enhanced delivery (CED), we tested if convective flow alters glioma invasion in vivo using the syngeneic GL261 mouse model of glioblastoma. We first confirmed that GL261 invasion in vitro increased under flow in a CXCR4-CXCL12 dependent manner. Additionally, approximately 65.4% and 6.59% of GL261 express CXCR4 and CXCL12 in vivo, respectively, with 3.38% expressing both. Inducing convective flow within implanted tumors indeed increased glioma cell invasion over untreated controls, and administering CXCR4 antagonist AMD3100 (5 mg/kg) effectively eliminated this response. Therefore, glioma invasion is in fact stimulated by convective flow in vivo through CXCR4. We also analyzed patient samples to show that expression of CXCR4 and CXCL12 increase in patients following therapy. These results suggesting that targeting flow-stimulated invasion may prove beneficial as a second line of therapy, particularly in patients chosen to receive convection enhanced drug delivery.

cancer biology↗

bioRxiv2018

Applicability of Drug Response Metrics for Cancer Studies using Biomaterials

Bioengineers have built increasingly sophisticated models of the tumor microenvironment in which to study cell-cell interactions, mechanisms of cancer growth and metastasis, and to test new potential therapies. These models allow researchers to culture cells in conditions that include features of the in vivo tumor microenvironment (TME) implicated in regulating cancer progression, such as ECM stiffness, integrin binding to the ECM, immune and stromal cells, growth factor and cytokine depots, and a 3D geometry more representative of the TME than tissue culture polystyrene (TCPS). These biomaterials could be particularly useful for drug screening applications to make better predictions of efficacy, offering better translation to preclinical in vivo models and clinical trials. However, it can be challenging to compare drug response reports across different platforms and conditions in the current literature. This is, in part, as a result of inconsistent reporting and use of drug response metrics, and vast differences in cell growth rates across a large variety of biomaterial design. This perspective paper attempts to clarify the definitions of drug response measurements used in the field, and presents examples in which these measurements can and cannot be applied. We suggest as best practice to include appropriate controls, always measure the growth rate of cells in the absence of drug, and follow our provided \"decision tree\" matrix when reporting drug response metrics.

bioengineering↗