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Comparison of Expression and Proliferative Effect of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its Receptors on Human Astrocytoma Cell Lines

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide considered to be a potent regulator of astrocytes. It has been reported that PACAP also affects astrocytoma cell properties, but the proliferative effects of this peptide in previous reports were inconsistent. The purpose of this study was to search for correlations between malignant potential, PACAP/PACAP receptor expression, and the proliferative potential of four astrocytoma cell lines (KNS-81, KINGS-1, SF-126, and YH-13). Immunohistochemical observations were performed using astrocyte lineage markers with a view to establishing malignant potential, which is inversely correlated to differentiation status in astrocytoma cells. YH-13 showed the most undifferentiated astrocyte-like status, and was immunopositive to a cancer stem cell marker, CD44. These observations suggest that YH-13 is the most malignant of the astrocytoma cell lines tested. Moreover, the strongest PAC1-R immunoreactivity was observed in YH-13 cells. Using real-time PCR analysis, no significant differences among cell lines were detected with respect to PACAP mRNA, but PAC1-R and VPAC1-R mRNA levels were significantly increased in YH-13 cells compared with the other cell lines. Furthermore, when cell lines were treated with PACAP (10−11 M) for 3 days, the YH-13 cell line, but not of the other cell lines, exhibited a significantly increased cell number. These results suggest that PACAP receptor expression is correlated with the malignant and proliferative potential of astrocytoma cell lines.

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Acknowledgments

This work was supported by Grants-in Aid for Scientific Research (KAKENHI: 23249079, 24592681, and 24592680) and by the MEXT-Support Program for the Strategic Research Foundation at Showa University (2012-16).

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Authors and Affiliations

  1. Department of Anatomy, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan

    Tomoya Nakamachi, Kouichi Sugiyama, Jun Watanabe, Nori Imai, Nobuyuki Kagami, Motohide Hori & Seiji Shioda

  2. Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, Toyama, Toyama, Japan

    Tomoya Nakamachi

  3. Center for Biotechnology, Showa University, Shinagawa-Ku, Tokyo, 142-8555, Japan

    Jun Watanabe & Satoru Arata

Authors
  1. Tomoya Nakamachi
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  2. Kouichi Sugiyama
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  3. Jun Watanabe
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  4. Nori Imai
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  5. Nobuyuki Kagami
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  6. Motohide Hori
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  7. Satoru Arata
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  8. Seiji Shioda
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Corresponding author

Correspondence to Seiji Shioda.

Additional information

Presented at the 11th International Symposium on VIP, PACAP, and Related Peptides.

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Nakamachi, T., Sugiyama, K., Watanabe, J. et al. Comparison of Expression and Proliferative Effect of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its Receptors on Human Astrocytoma Cell Lines. J Mol Neurosci 54, 388–394 (2014). https://doi.org/10.1007/s12031-014-0362-z

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  • DOI: https://doi.org/10.1007/s12031-014-0362-z

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