TGF-beta and BMP7 interactions in tumour progression and bone metastasis.
The skeleton is the second most frequent site of metastasis. However, only a restricted number of solid cancers, especially those of the breast and prostate, are responsible for the majority of the bone metastases. Metastatic bone disease is a major cause of morbidity, characterised by severe pain and high incidence of skeletal and haematopoietic complications (fractures, spinal cord compression and bone marrow aplasia) requiring hospitalisation. Despite the frequency of skeletal metastases, the molecular mechanisms for their propensity to colonise bone are poorly understood and treatment options are often unsatisfactory. TGF-beta and the signalling pathway it controls appears to play major roles in the pathogenesis of many carcinomas, both in their early stages, when TGF-beta acts to arrest growth of many cell types, and later in cancer progression when it contributes, paradoxically, to the phenotype of tumour invasiveness. Here we discuss some novel insights of the TGF-beta superfamily-including BMPs and their antagonists-in the formation of bone metastasis. Increasing evidence suggests that the TGF-beta superfamily is involved in bone homing, tumour dormancy, and development of micrometastases into overt bone metastases. The established role of TGF-beta/BMPs and their antagonists in epithelial plasticity during embryonic development closely resembles neoplastic processes at the primary site as well as in (bone) metastasis. For instance, the tumour-stroma interactions occurring in the tissue of cancer origin, including epithelium-to-mesenchyme transition (EMT), bear similarities with the role of bone matrix-derived TGF-beta in skeletal metastasis formation.
Buijs
Jeroen T
JT
Department of Endocrinology, Leiden University Medical Centre, Leiden, The Netherlands.
Henriquez
Niek V
NV
van Overveld
Petra G M
PG
van der Horst
Geertje
G
ten Dijke
Peter
P
van der Pluijm
Gabri
G
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D001859:Bone Neoplasms / Q000556:secondary*; D018450:Disease Progression; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology*; D011485:Protein Binding; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta