CMTM5 is reduced in prostate cancer and inhibits cancer cell growth in vitro and in vivo

Clin Transl Oncol. 2015 Jun;17(6):431-7. doi: 10.1007/s12094-014-1253-z. Epub 2014 Nov 12.

Abstract

Purpose: A novel tumor suppressor CKLF-like MARVEL transmembrane domain-containing member 5 (CMTM5) is reduced or undetectable in many kinds of cancers and inhibits tumor cells' malignant features. To explore its role in prostate cancer (PCa), we detected its expression patterns in prostate tissues and PCa cells, and determined its anti-proliferation functions in PCa cells in vitro and in vivo.

Methods: The expression of CMTM5 in prostate tissue microarray, specimens and cell lines was evaluated by immunohistochemistry and Western blot, respectively. After being transfected with CMTM5 adenovirus or vector, the proliferation and migration of DU145 cells were detected by MTT assay and transwell assay, respectively. Furthermore, the effects of CMTM5 on tumor growth were performed in nude mice xenograft in vivo.

Results: We found CMTM5 was reduced in PCa tissues and cells compared with BPH tissues, and its expression in PCa tissues was related to the Gleason score. Moreover, after being transfected with adenovirus, ectopic expression of CMTM5-v1 in DU145 cells led to significant inhibition of cell proliferation and migration compared with the control, which may be attributed to decreased Akt activity. Finally, restoration of CMTM5 significantly suppressed tumor growth in vivo.

Conclusions: These results indicate that CMTM5 is down-regulated in PCa and exhibit tumor suppressor activities in androgen-independent PCa cells. Loss of CMTM5 protein may be contributed to the development of PCa and it is a potential therapeutic target for castration-resistant prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Blotting, Western
  • Cell Proliferation
  • Chemokines / biosynthesis*
  • Down-Regulation
  • Heterografts
  • Humans
  • Immunohistochemistry
  • MARVEL Domain-Containing Proteins / biosynthesis*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Tissue Array Analysis
  • Tumor Suppressor Proteins / biosynthesis*

Substances

  • CMTM5 protein, human
  • Chemokines
  • MARVEL Domain-Containing Proteins
  • Tumor Suppressor Proteins