TY - JOUR
T1 - A liquid fraction of extracellular matrix inhibits glioma cell viability in vitro and in vivo
AU - Murdock, Mark H.
AU - Hussey, George S.
AU - Chang, Jordan T.
AU - Hill, Ryan C.
AU - Nascari, David G.
AU - Rao, Aparna V.
AU - Hansen, Kirk C.
AU - Foley, Lesley M.
AU - Hitchens, T. Kevin
AU - Amankulor, Nduka M.
AU - Badylak, Stephen F.
N1 - Publisher Copyright:
© 2022 Murdock et al.
PY - 2022
Y1 - 2022
N2 - Suppressive effects of extracellular matrix (ECM) upon various cancers have been reported. Glioblastoma multiforme has poor prognosis and new therapies are desired. This work investigated the effects of a saline-soluble fraction of urinary bladder ECM (ECM-SF) upon glioma cells. Viability at 24 hours in 1, 5, or 10 mg/mL ECM-SF-spiked media was evaluated in primary glioma cells (0319, 1015, 1119), glioma cell lines (A172, T98G, U87MG, C6), and brain cell lines (HCN-2, HMC3). Viability universally decreased at 5 and 10 mg/mL with U87MG, HCN-2, and HCM3 being least sensitive. Apoptosis in 0319 and 1119 cells was confirmed via NucView 488. Bi-weekly intravenous injection of ECM-SF (120 mg/kg) for 10 weeks in Sprague-Dawley rats did not affect weight, temperature, complete blood count, or multi-organ histology (N = 5). Intratumoral injection of ECM-SF (10 uL of 30 mg/ mL) at weeks 2–4 post C6 inoculation in Wistar rats increased median survival from 24.5 to 51 days (hazard ratio for death 0.22) and decreased average tumor volume at time of death from 349 mm3 to 90 mm3 over 10 weeks (N = 6). Mass spectrometry identified 2,562 protein species in ECM-SF, parent ECM, and originating tissue. These results demonstrate the suppressive effects of ECM on glioma and warrant further study.
AB - Suppressive effects of extracellular matrix (ECM) upon various cancers have been reported. Glioblastoma multiforme has poor prognosis and new therapies are desired. This work investigated the effects of a saline-soluble fraction of urinary bladder ECM (ECM-SF) upon glioma cells. Viability at 24 hours in 1, 5, or 10 mg/mL ECM-SF-spiked media was evaluated in primary glioma cells (0319, 1015, 1119), glioma cell lines (A172, T98G, U87MG, C6), and brain cell lines (HCN-2, HMC3). Viability universally decreased at 5 and 10 mg/mL with U87MG, HCN-2, and HCM3 being least sensitive. Apoptosis in 0319 and 1119 cells was confirmed via NucView 488. Bi-weekly intravenous injection of ECM-SF (120 mg/kg) for 10 weeks in Sprague-Dawley rats did not affect weight, temperature, complete blood count, or multi-organ histology (N = 5). Intratumoral injection of ECM-SF (10 uL of 30 mg/ mL) at weeks 2–4 post C6 inoculation in Wistar rats increased median survival from 24.5 to 51 days (hazard ratio for death 0.22) and decreased average tumor volume at time of death from 349 mm3 to 90 mm3 over 10 weeks (N = 6). Mass spectrometry identified 2,562 protein species in ECM-SF, parent ECM, and originating tissue. These results demonstrate the suppressive effects of ECM on glioma and warrant further study.
KW - brain cancer
KW - dynamic reciprocity
KW - extracellular matrix
KW - glioma treatment
KW - tissue organization field theory
UR - http://www.scopus.com/inward/record.url?scp=85127068485&partnerID=8YFLogxK
U2 - 10.18632/ONCOTARGET.28203
DO - 10.18632/ONCOTARGET.28203
M3 - Article
C2 - 35198102
AN - SCOPUS:85127068485
SN - 1949-2553
VL - 13
SP - 426
EP - 438
JO - Oncotarget
JF - Oncotarget
IS - 1
ER -