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Aberrant cAMP Metabolism in NF1 Malignant Peripheral Nerve Sheath Tumor Cells

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Abstract

Malignant peripheral nerve sheath (MPNST) cell lines derived from patients with neurofibromatosis type 1 (NF!) were found to have basal cAMP levels which are two-fold higher than cAMP levels in normal human adult Schwann cells (nHSC). PCR analysis also revealed that normal adult human Schwann cells express mRNA for types Ill, IV, and IX adenylyl cyclase (AC) while NF1 MPNST cells express AC mRNA of types II, V, and VIII in addition to expressing all the isoforms of normal adult human Schwann cells. Further PCR analysis revealed that NF1 MPNST lines express mRNA for EP2 and EP4 prostaglandin receptors whereas nHSC only express mRNA for the EP2 receptor. Exogenous prostaglandins alone or in combination with PDGF BB induced greater increases in cAMP levels and proliferation of NF1 MPNST cells compared to nHSC. We conclude that aberrant cAMP signaling in NF1 MPNST cells contributes to tumor formation in NF1 patients.

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Acknowledgments

This research was supported by US Army Medical Research and Material Command; (Contact grant number: DAMD17-98-8607). Salary support for G.H.D.V. was provided by a Career Research Health Science Award from the Department of Veterans Affairs. The authors thank Julie Litz for secretarial assistance. We are honored to make this contribution in tribute to the career of Robert K. Yu who we have been known for many years. Our association began over 40 years ago in the Saul Korey Department of Neurology at the Albert Einstein College of Medicine where we both carried out very enjoyable and productive postdoctoral studies. Bob also served as my Chairman for 7 years at the Medical College of Virginia. He is well known in neurochemistry for his pioneering work in the field of glycosphingolipids. His encouragement and hospitality have been a positive factor to myself and many others with whom he interacted over the years. His warm personality and helpful insights have been also been a blessing to many. On a more personal note he has been a gentleman and true friend to me and many others over the years. We wish him continued success and health in his continuing quest to understand the biological function of the complex glycosphingolipids which he continues to investigate.

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Authors and Affiliations

  1. Research 151, Hines VA Hospital, Hines, IL, 60141, USA

    Ian Dang

  2. Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL, 60153, USA

    Ian Dang

  3. Research 151, McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA, 23249, USA

    George H. De Vries

  4. Department of Anatomy and Neurobiology, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA, 23298-0709, USA

    George H. De Vries

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  1. Ian Dang
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Correspondence to George H. De Vries.

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Special Issue: In Honor of Dr. Robert Yu.

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Dang, I., De Vries, G.H. Aberrant cAMP Metabolism in NF1 Malignant Peripheral Nerve Sheath Tumor Cells. Neurochem Res 36, 1697–1705 (2011). https://doi.org/10.1007/s11064-011-0433-2

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