The potential of neurotensin secreted from neuroendocrine tumor cells to promote gelsolin-mediated invasiveness of prostate adenocarcinoma cells.

Kohei Hashimoto, Yuki Kyoda, Toshiaki Tanaka, Toshihiro Maeda, Ko Kobayashi, Kohsuke Uchida, Hiroshi Kitamura, Koichi Hirata, Taiji Tsukamoto, Naoya Masumori

Index: Lab. Invest. 95(3) , 283-95, (2015)

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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.