Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion

Liu, Yongqiang; Yuelling, Larra W.; Wang, Yuan; Du, Fang; Gordon, Renata E.; O’Brien, Jenny A.; Ng, Jessica M.Y.; Robins, Shannon; Lee, Eric H.; Liu, Hailong; Curran, Tom; Yang, Zeng-jie

doi:10.1158/0008-5472.can-17-1463

Cited by 52 publications

(93 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The astrocyte secretome is diverse and thus, there are likely a combination of factors in the ACM influencing the MB phenotypes. CCL2, SHH, and IL-4 are astrocyte-secreted factors which have been shown to promote MB phenotypes [8,9,42]. Interestingly, CCL2 secretion from astrocytes [9] was induced by chemotherapy and radiation-induced inflammation and necroptosis in astrocytes.…”

Section: Plos Onementioning

confidence: 99%

“…Previously, we have shown that astrocytes influence breast cancer cell invasion and facilitates its metastasis to the brain [6,7]. In primary brain tumors, such as MB, tumor-associated astrocytes have been found to secrete sonic hedgehog (SHH), which directly increased Nestin expression and proliferation of MB cells derived from a genetic mouse model of SHH MB [8]. Metastatic MB tumor-associated astrocytes were also recently identified to secrete chemokine C-C ligand 2 (CCL2), which enriched stem cell properties in MB cells, including expression of CD133 [9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Astrocytes influence medulloblastoma phenotypes and CD133 surface expression

et al. 2020

View full text Add to dashboard Cite

The medulloblastoma (MB) microenvironment is diverse, and cell-cell interactions within this milieu is of prime importance. Astrocytes, a major component of the microenvironment, have been shown to impact primary tumor cell phenotypes and metastasis. Based on proximity of MB cells and astrocytes in the brain microenvironment, we investigated whether astrocytes may influence MB cell phenotypes directly. Astrocyte conditioned media (ACM) increased Daoy MB cell invasion, adhesion, and in vivo cellular protrusion formation. ACM conditioning of MB cells also increased CD133 surface expression, a key cancer stem cell marker of MB. Additional neural stem cell markers, Nestin and Oct-4A, were also increased by ACM conditioning, as well as neurosphere formation. By knocking down CD133 using short interfering RNA (siRNA), we showed that ACM upregulated CD133 expression in MB plays an important role in invasion, adhesion and neurosphere formation. Collectively, our data suggests that astrocytes influence MB cell phenotypes by regulating CD133 expression, a key protein with defined roles in MB tumorgenicity and survival.

show abstract

Section: Plos Onementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Astrocytes influence medulloblastoma phenotypes and CD133 surface expression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…This effect still required SMO and it was blocked by SMO inhibitors [26]. The source of SHH in vivo was shown to be tumour-associated astrocytes.…”

Section: The Non-canonical Hedgehog Pathwaymentioning

confidence: 99%

Reproducibility of academic preclinical translational research: lessons from the development of Hedgehog pathway inhibitors to treat cancer

Curran¹

2018

Open Biol.

Self Cite

View full text Add to dashboard Cite

Academic translational research is growing at a great pace at a time in which questions have been raised about the reproducibility of preclinical findings. The development of Hedgehog (HH) pathway inhibitors for the treatment of cancer over the past two decades offers a case study for understanding the root causes of failure to predict clinical outcomes arising from academic preclinical translational research. Although such inhibitors were once hoped to be efficacious in up to 25% of human cancer, clinical studies showed responses only in basal cell carcinoma and the HH subtype of medulloblastoma. Close examination of the published studies reveals limitations in the models used, lack of quantitative standards, utilization of high drug concentrations associated with non-specific toxicities and improper use of cell line and mouse models. In part, these issues arise from scientific complexity, for example, the failure of tumour cell lines to maintain HH pathway activity in vitro, but a greater contributing factor appears to be the influence of unconscious bias. There was a strong expectation that HH pathway inhibitors would make a profound impact on human cancer and experiments were designed with this assumption in mind.

show abstract

“…Experiments performed in triplicate showed consistent results. Compared with control, *P < 0.05 because of high specificity for tumor cells and low toxicity to normal tissue [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Prediction and identification of novel HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from endocan

Shao¹,

Liu²,

Yang³

et al. 2020

J Inflamm

View full text Add to dashboard Cite

Background: Prediction and identification of cytotoxic T lymphocyte (CTL) epitopes from tumor associated antigens is a crucial step for the development of tumor immunotherapy strategy. Endocan has been identified as antigen overexpressed in various tumors. Methods: In this experiment, we predicted and identified HLA-A2-restricted CTL epitopes from endocan by using the following procedures. Firstly, we predicted the epitopes from the amino acid sequence of endocan by computer-based methods; Secondly, we determined the affinity of the predicted peptide with HLA-A2.1 molecule by peptide-binding assay; Thirdly, we elicited the primary T cell response against the predicted peptides in vitro; Lastly, we tested the specific CTLs toward endocan and HLA-A2.1 positive target cells. Results: These data demonstrated that peptides of endocan containing residues 4-12 and 9-17 could elicit specific CTLs producing interferon-γ and cytotoxicity. Conclusions: Therefore, our findings suggested that the predicted peptides were novel HLA-A2.1-restricted CTL epitopes, and might provide promising target for tumor immunotherapy.

show abstract

Astrocytes Promote Medulloblastoma Progression through Hedgehog Secretion

Cited by 52 publications

References 52 publications

Astrocytes influence medulloblastoma phenotypes and CD133 surface expression

Astrocytes influence medulloblastoma phenotypes and CD133 surface expression

Reproducibility of academic preclinical translational research: lessons from the development of Hedgehog pathway inhibitors to treat cancer

Prediction and identification of novel HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from endocan

Contact Info

Product

Resources

About