Document Detail

TGFβ(1) -Endo180 dependent collagen deposition is dysregulated at the tumour-stromal interface in bone metastasis.
MedLine Citation:
PMID:  22072289     Owner:  NLM     Status:  Publisher    
Cellular niches in adult tissue can harbour dysregulated microenvironments that become the driving force behind disease progression. The major environmental change when metastatic cells arrive in the bone is the destruction of mineralised type I collagen matrix. Once metastatic niches establish in bone the invading tumour cells initiate a vicious cycle of osteolytic lesion formation via the dysregulation of paracrine signals and uncoupling of normal bone resorption and production. Here we report that the collagen receptor Endo180 (CD280, MRC2, uPARAP) participates in collagen deposition by primary human osteoblasts during de novo osteoid formation. This newly recognised function of Endo180 was suppressed in osteoblasts following heterotypic direct cell-cell contact in coculture with prostate tumour cells. Reciprocal Endo180 upregulation in osteolytic prostate tumour cells (PC3 and DU145) followed their direct contact with osteoblasts and promoted de novo collagen internalisation, which is a previously characterised function of the constitutively recycling Endo180 receptor. The osteoblastic suppression and tumour cell associated enhancement of Endo180 expression were equally sustained in these direct cocultures. These findings are the first to demonstrate that increased tumour cell participation in collagen degradation and decreased collagen formation by osteoblasts in the osteolytic microenvironment are linked to the divergent regulation of a collagen-binding receptor. Immunohistochemical analysis of core biopsies from bone metastasis revealed higher levels of Endo180 expression in tumour cell foci than cells in the surrounding stroma. Additional experiments in prostate cell-osteoblast cocultures indicate that divergent regulation of Endo180 is the result of dysregulated TGFβ(1) -signalling. The findings of this study provide a rationale for targeting collagen remodelling by Endo180 in bone metastases and other collagen matrix pathologies. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Matthew P Caley; Giolanta Kogianni; Adam Adamarek; Julian H Gronau; Mercedes Rodriguez-Teja; Ana-Violeta Fonseca; Francesco Mauri; Ann Sandison; Johng S Rhim; Carlo Palmieri; Justin P Cobb; Jonathan Waxman; Justin Sturge
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-10
Journal Detail:
Title:  The Journal of pathology     Volume:  -     ISSN:  1096-9896     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Department of Surgery & Cancer, Imperial College London, UK.
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