SPARCL1 suppresses metastasis in prostate cancer

Mol Oncol. 2013 Dec;7(6):1019-30. doi: 10.1016/j.molonc.2013.07.008. Epub 2013 Jul 20.

Abstract

Purpose: Metastasis, the main cause of death from cancer, remains poorly understood at the molecular level.

Experimental design: Based on a pattern of reduced expression in human prostate cancer tissues and tumor cell lines, a candidate suppressor gene (SPARCL1) was identified. We used in vitro approaches to determine whether overexpression of SPARCL1 affects cell growth, migration, and invasiveness. We then employed xenograft mouse models to analyze the impact of SPARCL1 on prostate cancer cell growth and metastasis in vivo.

Results: SPARCL1 expression did not inhibit tumor cell proliferation in vitro. By contrast, SPARCL1 did suppress tumor cell migration and invasiveness in vitro and tumor metastatic growth in vivo, conferring improved survival in xenograft mouse models.

Conclusions: We present the first in vivo data suggesting that SPARCL1 suppresses metastasis of prostate cancer.

Keywords: CaP; GFP-positive PC3-Luc cells expressing empty control vector; GFP-positive PC3-Luc cells overexpressing SPARCL1; Gene expression signature; H.E.; IC; IHC; IVIS; Immunohistochemistry; Intracardiac; Meta-analysis; Metastasis; OX; PC3-Luc; PC3-luc/EV; PC3-luc/SPARCL1; Prostate cancer; SCID; SPARCL1; SPARCL1 function in vivo; Severe combined immunodeficient; cancer of the prostate gland; hematoxylin and eosin; in vivo Imaging System; orthotopic xenografting; secreted protein acidic and rich in cysteine-like 1; the bioluminescent human prostate carcinoma cell line.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins / biosynthesis*
  • Calcium-Binding Proteins / genetics
  • Cell Line, Tumor
  • Extracellular Matrix Proteins / biosynthesis*
  • Extracellular Matrix Proteins / genetics
  • Gene Expression Regulation, Neoplastic*
  • Heterografts
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Mice
  • Mice, SCID
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • SPARCL1 protein, human
  • Tumor Suppressor Proteins