title: The potential of neurotensin secreted from neuroendocrine tumor cells to promote gelsolin-mediated invasiveness of prostate adenocarcinoma cells.
abstract: Neuroendocrine (NE) cells in prostate cancer have been shown to be associated with the progression of prostate cancer. However, little is known about the molecular basis of this association. We have previously demonstrated that NE cells promote metastasis of a human prostate cancer cell line (LNCaP) with overexpression of the gelsolin gene. The purpose of this study was to investigate the interactions between NE cells and LNCaP cells and the involvement of gelsolin in contributing to the invasive potential of LNCaP cells. In addition, we examined whether neurotensin induced gelsolin-mediated invasion. We used the NE cell line NE-CS that was established from the prostate of the LPB-Tag 12T-10 transgenic mouse. Small interfering RNA (siRNA) targeting gelsolin or not targeting it was transfected into LNCaP cells. Cell invasion was assessed by Matrigel invasion assay. The supernatant of NE-CS cells and neurotensin induced the transformation of LNCaP cells. Neurotensin was observed in the supernatant of NE-CS cells but not in LNCaP cells. The siRNA targeting of gelsolin resulted in inhibition of invasion of LNCaP cells in the culture medium with neurotensin added, and in the supernatant of NE-CS cells with epidermal growth factor. The invasive potential of LNCaP cells enhanced by neurotensin or the supernatant of NE-CS cells through neurotensin receptor 1 (NTSR1) was blocked by a phospholipase Cγ inhibitor and an intracellular calcium chelator, with concomitant gelsolin suppression. This study indicates that NE cells and neurotensin induce gelsolin-mediated invasion of LNCaP cells through NTSR1 activation.
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kyoda
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Urology, Sanjukai Hospital, Sapporo, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: First Department of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hirata
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Tsukamoto
authors.affiliation: Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Masumori
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology*; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D018358:Neuroendocrine Tumors / Q000235:genetics / Q000378:metabolism; D009496:Neurotensin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D018028:Receptors, Neurotensin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017077:Culture Media, Conditioned; D018260:Gelsolin; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin