TY - JOUR
T1 - Functional characterization of brain tumor-initiating cells and establishment of GBM preclinical models that incorporate heterogeneity, therapy, and sex differences
AU - Garcia, Cesar A.
AU - Bhargav, Adip G.
AU - Brooks, Mieu
AU - Suarez-Meade, Paola
AU - Mondal, Sujan K.
AU - Zarco, Natanael
AU - ReFaey, Karim
AU - Jentoft, Mark
AU - Middlebrooks, Erik H.
AU - Snuderl, Matija
AU - Carrano, Anna
AU - Guerrero-Cazares, Hugo
AU - Schiapparelli, Paula
AU - Sarabia-Estrada, Rachel
AU - Quiñones-Hinojosa, Alfredo
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research
PY - 2021/12
Y1 - 2021/12
N2 - Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rhTNFSF10 (rhTRAIL), and rhBMP4. All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.
AB - Glioblastoma (GBM) is the most common primary brain cancer in adults where tumor cell heterogeneity and sex differences influence clinical outcomes. Here, we functionally characterize three male and three female patient-derived GBM cell lines, identify protumorigenic BTICs, and create novel male and female preclinical models of GBM. Cell lines were evaluated on the following features: proliferation, stemness, migration, tumorigenesis, clinical characteristics, and sensitivity to radiation, TMZ, rhTNFSF10 (rhTRAIL), and rhBMP4. All cell lines were classified as GBM according to epigenetic subtyping, were heterogenous and functionally distinct from one another, and re-capitulated features of the original patient tumor. In establishing male and female preclinical models, it was found that two male-derived GBM cell lines (QNS108 and QNS120) and one female-derived GBM cell line (QNS315) grew at a faster rate in female mice brains. One male-derived GBM cell line (QNS108) decreased survival in female mice in comparison with male mice. However, no survival differences were observed for mice injected with a female-derived cell line (QNS315). In summary, a panel of six GBM patient-derived cell lines were functionally characterized, and it was shown that BTIC lines can be used to construct sex-specific models with differential phenotypes for additional studies.
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U2 - 10.1158/1535-7163.MCT-20-0547
DO - 10.1158/1535-7163.MCT-20-0547
M3 - Article
C2 - 34465594
AN - SCOPUS:85120704640
SN - 1535-7163
VL - 20
SP - 2585
EP - 2597
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 12
ER -