• Open Access

Implications of pleiotrophin in human PC3 prostate cancer cell growth in vivo

Authors

  • Sotiria Tsirmoula,

    1. Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras, Greece
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    • These authors contributed equally to this work.
  • Kostas Dimas,

    1. Laboratory of Pharmacology–Pharmacotechnology, Basic Sciences Center, Biomedical Research Foundation of Academy of Athens, Athens, Greece
    2. Department of Pharmacology, Faculty of Medicine, University of Thessaly, Larissa, Greece
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    • These authors contributed equally to this work.
  • Maria Hatziapostolou,

    1. Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras, Greece
    Current affiliation:
    1. Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, MA, USA
    2. Department of Immunobiology and Microbiology, Harvard Medical School, Boston, MA, USA
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  • Margarita Lamprou,

    1. Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras, Greece
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  • Panagiota Ravazoula,

    1. Department of Pathology, Patras University Hospital, Patras, Greece
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  • Evangelia Papadimitriou

    Corresponding author
    • Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, Patras, Greece
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To whom correspondence should be addressed.

E-mail: epapad@upatras.gr

Abstract

Pleiotrophin (PTN) is a heparin-binding growth factor with diverse functions related to tumor growth, angiogenesis, and metastasis. Pleiotrophin seems to have a significant role in prostate cancer cell growth and to mediate the stimulatory actions of other factors that affect prostate cancer cell functions. However, all studies carried out up to date are in vitro, using different types of human prostate cancer cell lines. The aim of the present work was to study the role of endogenous PTN in human prostate cancer growth in vivo. For this purpose, human prostate cancer PC3 cells were stably transfected with a plasmid vector, bearing the antisense PTN sequence, in order to inhibit PTN expression (AS-PC3). Migration, apoptosis, and adhesion on osteoblastic cells were measured in vitro. In vivo, PC3 cells were s.c. injected into male NOD/SCID mice, and tumor growth, survival rates, angiogenesis, apoptosis, and the number of metastasis were estimated. Pleiotrophin depletion resulted in a decreased migration capability of AS-PC3 cells compared with the corresponding mock-transfected or the non-transfected PC3 cells, as well as increased apoptosis and decreased adhesiveness to osteoblastic cells in vitro. In prostate cancer NOD/SCID mouse xenografts, PTN depletion significantly suppressed tumor growth and angiogenesis and induced apoptosis of cancer cells. In addition, PTN depletion decreased the number of metastases, providing a survival benefit for the animals bearing AS-PC3 xenografts. Our data suggest that PTN is implicated in human prostate cancer growth in vivo and could be considered a potential target for the development of new therapeutic approaches for prostate cancer.

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