292P - Inhibition of endothelial cell-specific molecule-1 promotes the tumorigenicity and metastasis of prostate cancer cells

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Basic Science
Prostate Cancer
Presenter Yi-Hsien Hsieh
Citation Annals of Oncology (2016) 27 (suppl_9): ix90-ix93. 10.1093/annonc/mdw584
Authors Y. Hsieh
  • Department Of Biochemistry, School Of Medicine, Chung Shan Medical University, Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, 402 - Taichung/TW

Abstract

Background

Endothelial cell-specific molecule-1 (ESM-1) is a secretory proteoglycan comprising a mature polypeptide of 165 amino acids and a single dermatan sulfate. The ESM-1 protein has been involved in proliferation and metastatic progression in multiple tumors. The aim of this study was to evaluate the biological role of ESM-1 in prostate cancer.

Methods

ESM1 expression has been determined by western blotting, qRT-PCR, and immunohistochemistry in the human prostate cell lines PC3, DU145, LNCaP, and 22Rv, and in human prostate tissue array. In this study, we identified shRNA-ESM1 to determine the role of ESM1 in prostate-cancer cell proliferation, migration, and invasion. Cell proliferative ability was measured by MTT, colony-formation, and cell-cycle analysis. The role of ESM1 in prostate-cancer cell migration and invasion was analyzed by cell-migration assay and Matrigel invasion assay. The effect of ESM1 knockdown on tumorigenicity and metastasis were assessed in a subcutaneous xenograft and in vivo metastasis assay model.

Results

We found that ESM1 knockdown in prostate cancer cells resulted in increased cell proliferation and colony formation ability response evidenced by decreased expression of p21 and increased expression of cyclin D1 in prostate cancer cells. Moreover, we revealed that knockdown ESM1 also induced the epithelial-mesenchymal transition (EMT), motility and invasiveness in accordance with the upregulated the MMP-9 expression, while downregulated the TIMP-1 expression. Recombinant human (Rh) TIMP-1 significantly attenuated ESM-1-mediated cell migration and invasion. Additionally, ESM-1 knockdown increased in vivo tumorigenicity and metastasis of prostate cancer cells.

Conclusions

These findings provide the first evidence that the imbalance of MMP-9/TIMP-1, is one of the regulation mechanisms by which ESM-1 promotes tumorigenicity and metastasis of prostate cancer cells

Clinical trial indentification

No

Legal entity responsible for the study

N/A

Funding

Chung Shan Medical Hospital, Taichung, Taiwan

Disclosure

All authors have declared no conflicts of interest.