Somatostatin analogue inhibits mobility of prostate carcinoma cells and SSTR2a is a prognostic and therapeutic biomarker for prostate carcinoma
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Tang, Xiao Yan, Takekoshi, Susumu, Itoh, Johbu, Shoji, Sunao, Umemura, Shinobu, Terachi, Toshiro, Osamura, Robert Yoshiyuki and Imark, Esther (2010) Somatostatin analogue inhibits mobility of prostate carcinoma cells and SSTR2a is a prognostic and therapeutic biomarker for prostate carcinoma. International Journal of Oncology, 37 (5). pp. 1077-1083. ISSN 1019-6439
Abstract
The somatostatin analogue (SA), Octreotide, has been used as a therapeutic reagent for somatostatin receptor type 2a (SSTR2a)-positive cancers. The purpose of this study is to detect SSTR2a in human prostate carcinomas and to elucidate the effects of SA on SSTR2a-positive prostate carcinoma cells to determine the potential of this drug as a new therapeutic method for advanced prostate carcinoma.
Material and Methods: Immunohistochemical study of SSTR2a was performed on 108 prostate carcinoma cases. RT-PCR analysis was performed on 11 needle biopsy and 3 metastatic cases. Proliferation, migration and invasion assays were performed by using SSTR2a-positive prostate cancer cells, DU145 and PC3, treated with SA and/or Rho-kinase inhibitor Y-27632. Morphological changes of prostate carcinoma cells were also examined by staining for vinculin, rhodamine phalloidin, and alpha tubulin.
Results: The study showed expression of SSTR2a in 13 of the 108 cases (12%); the histological grade (Gleason) and tumor stage of the prostate carcinoma were directly related to SSTR2a expression. Among the seven cases of lymph node (LN) metastasis, SSTR2a expression was markedly higher. SSTR2 mRNA was detected by RT-PCR in only 4 of 11 needle biopsy cases and 1 of 3 cases of LN metastasis.
Migration and invasion abilities of DU145 and PC3 cells were inhibited by SA in a dose-dependent manner. This inhibition was reversed by Y-27632. Morphological changes of the prostate cancer cells treated with SA and Y27632 corroborate the migration and invasion assays, although SA had no effect on proliferation of DU145 and PC3 cells.
Conclusion: SSTR2a is a potential prognostic factor for prostatic carcinoma. SA may be beneficial for patients with advanced prostate carcinoma or to protect from distal metastasis if they are positive for SSTR2a.
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| Date Deposited: | 13 Oct 2015 13:17 |
| Last Modified: | 13 Oct 2015 13:17 |
| URI: | https://oak.novartis.com/id/eprint/1584 |