Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells

Abstract

Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.

Human Medulloblastoma Cell Lines: Investigating on Cancer Stem Cell-Like Phenotype

“…Very recently, CD133-enriched cell population group 3 MB cells were more prone to form tumorspheres and more tumorigenic when compared to CD133-depleted cells, as demonstrated after in vitro and in vivo LDA [51]. Similar features (i.e., high proliferative activity, high colony formation efficiency, enhanced ability to generate tumorspheres enriched in CD133+ cells, as well as higher tumorigenicity in vivo) have been demonstrated in USP-13-Med cells, a new MB cell line with a profile more consistent with that of group 4 tumors, when compared to the DAOY cells [24].…”

“…To develop specific CSCs-targeting therapies, studies are needed using enriched and stable CSC cell populations. Given the relatively MB low incidence, the possibility of accessing patient-derived samples is extremely limited and furthermore, few MB cell lines are available in central repositories making it more complex to study this tumor compared to others [24]. Thus, the MB research area is greatly frustrated by the recognized difficulty in culturing and obtaining high amounts of primary patient-derived cells for in vitro studies.…”

High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells

“…The PDL of parental Daoy and USP13-Med cells, under the same experimental conditions, are known [52]. …”

Zika Virus Selectively Kills Aggressive Human Embryonal CNS Tumor Cells In Vitro and In Vivo

“…Three embryonal CNS tumor cell lines: DAOY (medulloblastoma, ATCC HTB-186), USP13-MED (medulloblastoma, inhouse established; ref. 8), and USP7-ATRT (atypical teratoid/ rhabdoid tumor, in-house established); three non-CNS tumor cell lines: MCF-7 (breast cancer, ATCC HTB-22), HCT-8 (colorectal cancer, ATCC CCL-244), and DU-145 (prostate cancer, derived from brain metastasis, ATCC HTB-81); one control human-induced pluripotent stem cell (hiPSC, C2535, in-house reprogrammed)-derived NPCs and neurons were analyzed. Detailed information regarding the generation and characterization of hiPSCs, NPCs, and neurons is provided in Supplementary Materials.…”