Thrombospondin 1: a multifunctional protein implicated in the regulation of tumor growth.
Crit Rev Oncol Hematol
; 49(3): 245-58, 2004 Mar.
Article
em En
| MEDLINE
| ID: mdl-15036264
ABSTRACT
Thrombospondins belong to a family of extracellular matrix (ECM) proteins widely found from embryonic to adult tissues. The modular structure of thrombospondins contains a series of peptide sequences implicated in a multiplicity of biological functions. Extracellular matrix undergoes important alterations under proteolysis that occurs in pathological processes like tumorigenesis. An elevated secretion of thrombospondin 1 (TSP1) is often observed in tumors and is sometimes considered as a predictive factor. However, the role of TSP1 in cancer progression remains controversial and must be carefully apprehended. The regulation of cell adhesion, proliferation, apoptosis by TSP1 is examined in the present review and it is clear from the literature and from our investigations that TSP1 presents both stimulatory and inhibitory effects. The exposition of cryptic sites upon conformational changes can partially explain this contradiction. More interestingly, the analysis of TSP1-directed intracellular signaling pathways activated through specific receptors or supramolecular receptors docking systems may be useful to discriminate the precise function of TSP1 in tumor progression. The central role played by TSP1 in the control of matrix-degrading enzyme activation and catabolism reveals attractive tracks of research and highlights the involvement of the lipoprotein receptor-related protein (LRP) receptor in these events. Therefore, TSP1-derived peptides constitute a source of potentially active matrikins which could provide essential tools in cancer therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Trombospondina 1
/
Invasividade Neoplásica
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Crit Rev Oncol Hematol
Ano de publicação:
2004
Tipo de documento:
Article