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Differential expression of the alpha2 chain of the interleukin-13 receptor in metastatic human prostate cancer ARCaPM cells.

ABSTRACT: The alpha2 chain of the interleukin-13 receptor (IL13Ralpha2) is a high-affinity receptor and a candidate target for cytotoxic killing of cancer cells. Availability of a human prostate cancer cell line with high level of IL13Ralpha2 expression will facilitate the development of therapeutic modalities.ARCaP(E) and ARCaP(M) human prostate cancer cell lines were subjected to comparative analyses of gene expression. Expression of the IL13Ralpha2 protein was confirmed by Western blotting and immunostaining. IL13Ralpha2 proteins in xenograft tumors and clinical human prostate cancer specimens were detected by specific antibodies. LNCaP prostate cancer cells stably transfected with IL13Ralpha2 were examined for accelerated growth in athymic mice.We found that IL13Ralpha2 proteins could be detected in both the ARCaP(E) and ARCaP(M) cells, but the expression level in ARCaP(M) was more than 17-fold higher than in ARCaP(E) cells. Importantly, the ARCaP lineage represented the only human prostate cancer cell line that expresses IL13Ralpha2 proteins at the level detectable by Western blotting. Expression of IL13Ralpha2 was accompanied by resistance to the anti-tumor activity of interleukin-13 (IL-13). ARCaP cells were found to be insensitive to growth inhibition upon IL-13 treatment, while overexpression of IL13Ralpha2 in LNCaP cells promoted intratibial tumor growth in athymic mice.Differential IL13Ralpha2 expression may account for the high tumorigenic and metastatic potential of ARCaP(M) cells. The unique expression of IL13Ralpha2 makes ARCaP lineage an attractive model for evaluating the targeting efficacy of therapeutic agents based on IL13Ralpha2 protein expression.

SUBMITTER: He H

PROVIDER: S-EPMC3180892 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Differential expression of the alpha2 chain of the interleukin-13 receptor in metastatic human prostate cancer ARCaPM cells.

He Hui H Xu Jianchun J Nelson Peter S PS Marshall Fray F FF Chung Leland W K LW Zhau Haiyen E HE He Dalin D Wang Ruoxiang R

The Prostate 20100601 9

<h4>Background</h4>The alpha2 chain of the interleukin-13 receptor (IL13Ralpha2) is a high-affinity receptor and a candidate target for cytotoxic killing of cancer cells. Availability of a human prostate cancer cell line with high level of IL13Ralpha2 expression will facilitate the development of therapeutic modalities.<h4>Methods</h4>ARCaP(E) and ARCaP(M) human prostate cancer cell lines were subjected to comparative analyses of gene expression. Expression of the IL13Ralpha2 protein was confirm ...[more]

PMID: 20166133

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Project description:The objective of this study was to investigate IL13Ra2 expression in brainstem glioma (BSG) and its correlation with key markers, functions, and prognostic implications, evaluating its therapeutic potential. A total of 80 tumor samples from BSG patients were analyzed. Multiplex immunofluorescence was used to examine six markers-IL13Ra2, H3.3K27M, CD133, Ki67, HLA-1, and CD4-establishing relationships between IL13Ra2 and these markers. Survival analysis, employing Kaplan-Meier and Cox proportional hazard regression models, encompassed 66 patients with complete follow-up. RNA-Seq data from a previously published study involving 98 patients were analyzed using the DESeq2 library to determine differential gene expression between groups. Gene Ontology (GO) enrichment and single-sample gene set enrichment analysis (ssGSEA) via the clusterProfiler library were used to delineate the gene functions of differentially expressed genes (DEGs). Nearly all the BSG patients displayed varying IL13Ra2 expression, with 45.0% (36/80) exhibiting over a 20% increase. Elevated IL13Ra2 levels were notably observed in pontine gliomas, diffuse intrinsic pontine gliomas (DIPGs), H3F3A-mutant gliomas, and WHO IV gliomas. IL13Ra2 expression was strongly correlated with H3.3K27M mutant protein, Ki67, and CD133. Patients with IL13Ra2 expression >20% showed shorter overall survival compared to those with ≤20% IL13Ra2 expression. The Cox proportional hazard regression model identified H3F3A mutations, rather than IL13Ra2 expression, as an independent prognostic factor. Analysis of RNA-Seq data from our prior cohort confirmed IL13Ra2's correlation with H3.3, CD133, and Ki67 levels. Widespread IL13Ra2 expression in BSG, particularly elevated in the H3F3A mutant group, was strongly correlated with H3F3A mutations, increased proliferation, and heightened tumor stemness. IL13Ra2 represents a promising therapeutic target for BSGs, potentially benefiting patients with H3K27M mutations, DIPGs, WHO Grade IV, and pontine location-specific BSGs, particularly those with H3K27M mutations.

Dataset Information

Differential expression of the alpha2 chain of the interleukin-13 receptor in metastatic human prostate cancer ARCaPM cells.

Publications

Differential expression of the alpha2 chain of the interleukin-13 receptor in metastatic human prostate cancer ARCaPM cells.

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