TY  - JOUR
A1  - Stange, Lena
A1  - Lucia, Kristin Elizabeth
A1  - Ghori, Adnan
A1  - Vajkoczy, Peter
A1  - Czabanka, Marcus Alexander
A1  - Broggini, Thomas
T1  - LPPR5 Expression in Glioma Affects Growth, Vascular Architecture, and Sunitinib Resistance
T2  - International journal of molecular sciences
N2  - Despite intensive research, glioblastoma remains almost invariably fatal. Various promising drugs targeting specific aspects of glioma biology, in addition to or as an alternative to antiproliferative chemotherapy, were not successful in larger clinical trials. Further insights into the biology of glioma and the mechanisms behind the evasive-adaptive response to targeted therapies is needed to help identify new therapeutic targets, prognostics, or predictive biomarkers. As a modulator of the canonically oncogenic Rho-GTPase pathway, Lipid phosphate phosphatase-related protein type 5 (LPPR5) is pivotal in influencing growth, angiogenesis, and therapeutic resistance. We used a GL261 murine orthotopic allograft glioma model to quantify the tumor growth and to obtain tissue for histological and molecular analysis. Epicortical intravital epi-illumination fluorescence video microscopy of the tumor cell spheroids was used to characterize the neovascular architecture and hemodynamics. GL261-glioma growth was delayed and decelerated after LPPR5 overexpression (LPPR5OE). We observed increased tumor cell apoptosis and decreased expression and secretion of vascular endothelial growth factor A in LPPR5OE glioma. Hence, an altered micro-angioarchitecture consisting of dysfunctional small blood vessels was discovered in the LPPR5OE tumors. Sunitinib therapy eliminated these vessels but had no effect on tumor growth or apoptosis. In general, LPPR5 overexpression generated a more benign, proapoptotic glioma phenotype with delayed growth and a dysfunctional vascular architecture.
KW  - plppr5
KW  - lppr5
KW  - PRG5
KW  - antiangiogenic therapy resistance
KW  - sunitinib
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/80954
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-809544
SN  - 1422-0067
VL  - 23
IS  - 6, art. 3108
SP  - 1
EP  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -