| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Research Abstract |
1. We investigated the effect of 10 neuropeptides present in prostate including calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), substance P (SP), neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP), calcitonin (CT), leucine-enkephalin (L-ENK), methionine-enkephaline(M-ENK), glucagon and parathyroid hormone-related protein (PTH-rP) on the invasion of PC-3 and DU-145 prostate cancer cells through a reconstituted basement membrane (Matrigel) using a Transwell cell culture chamber assay. Both CGRP and GRP increased the invasive capacity of PC-3 cells, whereas SP inhibited it. Both CGRP and GRP also increased the haptotactic migration of tumor cells to fibronectin, but SP inhibited it. These three neuropeptides had no effect on either adhesion to fibronectin and laminin or on the gelatinolytic activities of MMP-9 in gelatin zymography, nor did they affect the growth of tumor cells at concentrations used in this study. CGRP, GRP and PTH-rP increased the invasive capacity of DU-145 cells. Some of prostatic neuropeptides may affect the effect of the invasion of prostate cancer cells.
2. Chromogranin A fragment (286-301) increased the invasive capacity of both PC-3 and DU-145 cells, whereas it had no significant effect of LNCaP cells. Chromogranin A fragment also increased the haptotactic migration of both PC-3 and DU-145 cells to fibronectin. Furthermore chromogranin A fragment increased the fibrinolytic activities of urokinase-type plasminogen activator (u-PA) in fibrin zymogram of both PC-3 and DU-145 cells and the expression of u-PA mRNA of PC-3 cells.
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