Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-9-22
pubmed:abstractText
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 metalloproteinase-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0965-0407
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17-31
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10451028-Cell Movement, pubmed-meshheading:10451028-Chemotaxis, pubmed-meshheading:10451028-Collagen, pubmed-meshheading:10451028-Collagenases, pubmed-meshheading:10451028-Culture Media, Conditioned, pubmed-meshheading:10451028-Culture Media, Serum-Free, pubmed-meshheading:10451028-Drug Combinations, pubmed-meshheading:10451028-Humans, pubmed-meshheading:10451028-Laminin, pubmed-meshheading:10451028-Male, pubmed-meshheading:10451028-Matrix Metalloproteinase 9, pubmed-meshheading:10451028-Neoplasm Invasiveness, pubmed-meshheading:10451028-Neoplasm Proteins, pubmed-meshheading:10451028-Osteoblasts, pubmed-meshheading:10451028-Prostatic Neoplasms, pubmed-meshheading:10451028-Proteoglycans, pubmed-meshheading:10451028-Tumor Cells, Cultured, pubmed-meshheading:10451028-Urokinase-Type Plasminogen Activator
pubmed:year
1999
pubmed:articleTitle
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.
pubmed:affiliation
Department of Experimental Medicine, Medical School, University of L'Aquila, Italy. festucci@univaq.it
pubmed:publicationType
Journal Article