The Cellular Retinoic Acid Binding Protein 2 Promotes Survival of Malignant Peripheral Nerve Sheath Tumor Cells

The American Journal of Pathology
Susan Fischer-HuchzermeyerAnja Harder

Abstract

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive neoplasms that commonly occur in patients with neurofibromatosis type 1 (NF1). Effective chemotherapy is not available. To characterize a therapeutic target for treatment, we investigated the role of cellular retinoic acid binding protein 2 (CRABP2) in MPNST in vitro. CRABP2 is a transcriptional co-activator of retinoic acid signaling. Although overexpression of CRABP2 is described in several cancers, it has not yet been studied in MPNSTs. We investigated CRABP2 expression in cultured Schwann cells and formalin-fixed, paraffin-embedded specimens of human peripheral nerve sheath tumors. A transient knockdown of CRABP2 was established in human NF1-associated MPNST cell lines (S462, T265, NSF1), and functional effects on viability, proliferation, apoptosis, and cytotoxicity were monitored. Finally, a 45-pathway reporter assay was performed in knockdown cells. Expression of CRABP2 was found in epithelium, fibroblasts, and tumor Schwann cells of skin, neurofibromas, and MPNSTs. In contrast, normal skin Schwann cells (NF1(+/-), NF1(-/-)) did not express CRABP2. In the absence of retinoic acid, MPNST cells depleted of CRABP2 had reduced viability and proliferation, induc...Continue Reading

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Citations

Apr 19, 2018·Expert Opinion on Therapeutic Targets·James A Walker, Meena Upadhyaya
Feb 6, 2020·Current Protein & Peptide Science·Xiaoyang JiaoEnmin Li
Jul 30, 2018·BMC Research Notes·Susan Fischer-HuchzermeyerAnja Harder
Oct 1, 2020·Food Science & Nutrition·Xinhong LiuXin Zhao

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