Osteoblasts modulate secretion of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in human prostate cancer cells promoting migration and matrigel invasion

Claudio Festuccia, Daniela Giunciuglio, Fulvio Guerra, Ida Villanova, Adriano Angelucci, Paola Manduca, Anna Teti, Adriana Albini, Mauro Bologna

Research output: Contribution to journalArticlepeer-review

Abstract

Prostate carcinoma (PRCA) cells metastasize to the skeleton with high frequency. Bone stores growth regulatory factors, which are released in active form during bone remodeling. We propose that bone cell-derived growth factors may induce the development of PRCA bone metastasis by recruiting tumor cells and increasing their proliferation in the bone microenvironment. Serum-free conditioned medium harvested from osteoblast cultures (OB CM) stimulated the in vitro chemotaxis of PRCA cells and invasion of a reconstituted basement membrane (Matrigel), suggesting enhanced invasive activity. Preosteoblastic cell CMs were less effective than CMs obtained from mature OB. CMs harvested from differentiated osteoblast cultures capable of matrix mineralization were more active compared to CMs from proliferating osteoblasts. OB CMs stimulated secretion of urokinase (uPA) and matrix melalloproteinase-9 (MMP-9). Inhibition of these matrix-degrading proteases by neutralizing antibodies and/or by inhibitors of their catalytic activity reduced Matrigel invasion. Secretion of uPA and activation of MMP-9 were most prominent by differentiated OB CMs with respect to poorly differentiated cells in vitro. These results are in agreement with several in vivo studies and indicate that factors produced during osteogenesis by bone cells stimulate PRCA cell chemotaxis and matrix proteases expression, thus representing potential targets for alternative therapies deterring the progression of PRCA metastasis to bone.

Original languageEnglish
Pages (from-to)17-31
Number of pages15
JournalOncology Research
Volume11
Issue number1
Publication statusPublished - 1999

Keywords

  • Bone metastasis
  • Metalloproteinase-9
  • Prostate cancer
  • Urokinase

ASJC Scopus subject areas

  • Cancer Research

Fingerprint Dive into the research topics of 'Osteoblasts modulate secretion of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP-9) in human prostate cancer cells promoting migration and matrigel invasion'. Together they form a unique fingerprint.

Cite this