Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural matrix protein.

Abstract

Abstract. The role of the latent TGF-[3 binding protein (LTBP) is unclear. In cultures of fetal rat calvarial cells, which form mineralized bonelike nodules, both LTBP and the TGF-[31 precursor localized to large fibrillar structures in the extracellular matrix. The appearance of these fibrillar structures preceded the appearance of type I collagen fibers. Plasmin treatment abolished the fibrillar staining pattern for LTBP and released a complex containing both LTBP and TGF-[3. Antibodies and antisense oligonucleotides against LTBP inhibited the formation of mineralized bonelike nodules in long-term fetal rat calvarial cultures. Immunohistochemistry of fetal and adult rat bone confirmed a fibrillar staining pattern for LTBP in vivo. These findings, together with the known homology of LTBP to the fibrillin family of proteins, suggest a novel function for LTBP, in addition to its role in matrix storage of latent TGF-~, as a structural matrix protein that may play a role in bone formation.

Latent Transforming Growth Factor-β (TGF-β) Binding Proteins: Orchestrators of TGF-β Availability

“…The description of an LTBP-2 adhesive activity (39) for melanoma cells indicates that LTBPs can have non-TGF-␤-dependent activities. However, interpretation of the results of Dallas et al (38) as demonstrating a direct effect of LTBP-1 can be criticized based upon lack of evidence that added TGF-␤ reached the target cells.…”

“…Dallas et al (38) published that antibodies to LTBP-1 blocked development of mineralized foci by rat calvarial cells. The antibody effect was not suppressed by addition of TGF-␤ but was replicated by treatment with an LTBP-1 antisense oligonucleotide.…”

Tissue elasticity and the ageing elastic fibre

“…The four known LTBPs are remarkably similar in structure to the fibrillins, and the predominance of multiple contiguous cbEGF domains and the possession of apparently unique TB modules in both protein families led to the proposal that collectively the LTBPs and fibrillins should be grouped into a fibrillin super-family (Hubmacher et al 2006;Hyytiainen et al 2004). LTBPs appear to fulfil dual roles as both structural components of the ECM (Dallas et al 1995) and as TGFβ trafficking molecules (Miyazono et al 1991). Furthermore, the association of LTBPs with fibrillin microfibrils (Raghunath et al 1998;Unsold et al 2001) and the perturbations of normal TGFβ signalling in FBN1-mutant mice led to the hypothesis that fibrillin microfibrils play a major role in maintaining tissue homeostasis via LTBP-mediated sequestration of TGFβ (Denton and Abraham 2001;Neptune et al 2003).…”

Homing of Cancer Cells to the Bone

“…PSA can cleave parathyroid hormone related peptide (PTHrP) at the amino terminus and could also potentially activate other growth factors such as TGF-β that are produced by prostate carcinomas [53][54][55][56]. Interestingly, over expression of PSA in osteosarcoma cell line Saos-2 results in induction of receptor activator of nuclear factor κ-B ligand (RANKL), runt-related transcription factor 2 (RUNX2) and wingless type (WNT) signaling all of which are important in bone remodeling, thus indirectly suggesting a role of PSA in prostate cancer metastasis [57].…”