Differential Glioma-Associated Tumor Antigen Expression Profiles of Human Glioma Cells Grown in Hypoxia

Abstract

Human U251 and D54 glioma cells were tested for expression of 25 glioma-associated tumor antigen precursor proteins (TAPP) under hypoxic (1% O2) or normoxic (21% O2) conditions. Hypoxic glioma cell lines increased their mRNA expression for nine TAPP (Aim2, Art-4, EphA2, EZH2, Fosl1, PTH-rP, Sox 11, Whsc2 and YKL-40), as assessed by quantitative reverse transcriptase real-time/polymerase chain reaction (qRT-PCR). Increased differences with three hypoxic-induced TAPP: EZH2, Whsc2 and YKL-40 were shown at the protein levels by fluorescent antibody staining and quantitative electrophoretic analysis. Two TAPP (MRP3 and Trp1) were down-regulated by hypoxia in glioma cell lines. Growing the glioma cells under hypoxia for 13 days, followed by returning them back to normoxic conditions for 7 days, and restored the original normoxic TAPP profile. Thus, hypoxia was an environmental factor that stimulated the transient expression of these antigens. Intracranial xenografts grown in nude mice derived from U251 cells that had been cultured under neurosphere stem cell conditions showed increased expression of Whsc2 or YKL-40, demonstrating that these in vitro properties of glioma also occur in vivo. Whsc2-specific cytotoxic T lymphocytes killed the hypoxic U251 glioma cells better than normoxic glioma cells. The antigens expressed by hypoxic tumor cells may be a better source of starting tumor material for loading dendritic cells for novel immunotherapy of glioma using tumor-associated antigens.

Overexpression miR‐211‐5p hinders the proliferation, migration, and invasion of thyroid tumor cells by downregulating SOX11

“…MicroRNAs (miRNAs) are a group of aroud‐22 nucleotide non‐coding small RNAs, and it is confirmed that they have a close association with many cancers . In the meantime, as one of the tumor antigenic precursor proteins (TAPP), SOX11 has also been confirmed to be related with many cancers . According to the prediction of miR‐base and our microarray assays, we predicted the target relationship between SOX11 and miR‐211‐5p.…”

“…revealed that SOX11 was overexpressed in aggressive fibromatosis cells and could contribute to the classification of aggressive fibromatosis . Besides, Ge et al . also claimed that SOX11 was at high expression level in human glioma cells and its underexpression suppressed the proliferation and invasion abilities of glioma cells.…”

Genome-wide DNA methylation assay reveals novel candidate biomarker genes in cervical cancer

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HCA519/TPX2: a potential T-cell tumor-associated antigen for human hepatocellular carcinoma

“…qRT‐PCR was performed using primers that detect various tumor antigen precursor proteins (TAPPs). 18S ribosomal RNA served as the internal control as we previously used 26,27…”