Association of extracellular matrix proteins fibulin‐1 and fibulin‐2 with fibronectin in bone marrow stroma

Gu, Yuchen; Nilsson, Kenneth; H, Eng; Ekblom, Marja

doi:10.1046/j.1365-2141.2000.02011.x

Cited by 30 publications

(30 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An example of such a protein is fibulin-2, a 1195-residue polypeptide preceded by a 26-residue signal peptide that mainly resides in the basement membranes and other connective tissue compartments (152). Fibulin-2 is expressed in heart, placenta, and ovarian tissues (153), and has been shown to link the cells to the basement membrane in epithelial (154) and hematopoietic cells (155). This linkage contributes to cell migration in epicardial cells during coronary vasculogenesis and angiogenesis (156), and in smooth muscle cells during atherosclerotic lesions (157).…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

Chan

Masui

Krakovska

et al. 2011

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Myogenesis is a well-characterized program of cellular differentiation that is exquisitely sensitive to the extracellular milieu. Systematic characterization of the myogenic secretome (i.e. the ensemble of secreted proteins) is, therefore, warranted for the identification of novel secretome components that regulate both the pluripotency of these progenitor mesenchymal cells, and also their commitment and passage through the differentiation program. Previously, we have successfully identified 26 secreted proteins in the mouse skeletal muscle cell line C2C12 (1). In an effort to attain a more comprehensive picture of the regulation of myogenesis by its extracellular milieu, quantitative profiling employing stable isotope labeling by amino acids in cell culture was implemented in conjunction with two parallel high throughput online reverse phase liquid chromatography-tandem mass spectrometry systems.In summary, 34 secreted proteins were quantified, 30 of which were shown to be differentially expressed during muscle development. Intriguingly, our analysis has revealed several novel up-and down-regulated secretome components that may have critical biological relevance for both the maintenance of pluripotency and the passage of cells through the differentiation program. In particular, the altered regulation of secretome components, including follistatin-like protein-1, osteoglycin, spondin-2, and cytokine-induced apoptosis inhibitor-1, along with consti-

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

Chan

Masui

Krakovska

et al. 2011

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…A number of constitutively downregulated genes have reported roles in cellular adhesion processes. These include: fibronectin 1 (FN1), a major ECM component required for integrin-mediated signalling (reviewed in Danen and Yamada, 2001); fibulin 2 (FBLN2), which colocalises with FN1 in vivo (Gu et al, 2000); and the tissue inhibitor of metalloproteinase 3 (TIMP 3), which is involved in regulating FN1 degradation (Fata et al, 2001). Given these changes, it is possible that ErbB-2 overexpression may alter the adhesive properties of these cells (see below).…”

Section: Global Changes In Gene Expressionmentioning

confidence: 99%

Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression

et al. 2004

View full text Add to dashboard Cite

Microarray analysis offers a powerful tool for studying the mechanisms of cellular transformation, although the correlation between mRNA and protein expression is largely unknown. In this study, a microarray analysis was performed to compare transcription in response to overexpression of the ErbB-2 receptor tyrosine kinase in a model mammary luminal epithelial cell system, and in response to the ErbB-specific growth factor heregulin b1. We sought to validate mRNA changes by monitoring changes at the protein level using a parallel proteomics strategy, and report a surprisingly high correlation between transcription and translation for the subset of genes studied. We further characterised the identified targets and relate differential expression to changes in the biological properties of ErbB-2-overexpressing cells. We found differential regulation of several key cell cycle modulators, including cyclin D2, and downregulation of a large number of interferon-inducible genes, consistent with increased proliferation of the ErbB-2-overexpressing cells. Furthermore, differential expression of genes involved in extracellular matrix modelling and cellular adhesion was linked to altered adhesion of these cells. Finally, we provide evidence for enhanced autocrine activation of MAPK signalling and the AP-1 transcription complex. Together, we have identified changes that are likely to drive proliferation and anchorage-independent growth of ErbB-2-overexpressing cancer cells.

show abstract

“…Fibulin-1 was purified with RIDAGTT peptide. Fibulin-1 is present in the stroma of several ovarian cancers and cysts (22) and in normal bone marrow stroma (23). It also makes breast cancer cells more resistant to doxorubicin (24).…”

Section: Discussionmentioning

confidence: 99%

Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors

Mandelin

Cardó-Vila

Driessen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We performed combinatorial peptide library screening in vivo on a novel human prostate cancer xenograft that is androgenindependent and induces a robust osteoblastic reaction in bonelike matrix and soft tissue. We found two peptides, PKRGFQD and SNTRVAP, which were enriched in the tumors, targeted the cell surface of androgen-independent prostate cancer cells in vitro, and homed to androgen receptor-null prostate cancer in vivo. Purification of tumor homogenates by affinity chromatography on these peptides and subsequent mass spectrometry revealed a receptor for the peptide PKRGFQD, α-2-macroglobulin, and for SNTRVAP, 78-kDa glucose-regulated protein (GRP78). These results indicate that GRP78 and α-2-macroglobulin are highly active in osteoblastic, androgen-independent prostate cancer in vivo. These previously unidentified ligand-receptor systems should be considered for targeted drug development against human metastatic androgen-independent prostate cancer.peptides | ligand receptors | phage display | GRP78 | tumor targeting A ndrogen deprivation remains the standard therapy for metastatic prostate cancer. Despite the favorable initial response, in most cases the disease progresses, becomes androgen-independent, and gives rise to soft tissue and osteoblastic bone metastases that ultimately lead to death (1, 2). Paradoxically, all currently available animal models of osteoblastic bone metastases are androgen dependent (3-6). The first (to our knowledge) human prostate cancer xenograft model that does not express androgen receptor but still induces a strong osteogenic response led Li et al. (7) to conclude that androgen receptor-null cells contribute to the castrate-resistant osteoblastic progression of prostate cancer and that targeting these cells will be critical in the treatment of prostate cancer bone metastases.In vivo phage display can be used to explore the surface of cells in their anatomical microenvironment (8)(9)(10)(11)(12)(13)(14). This technology enables the identification of molecular signatures that could allow targeted systemic delivery of therapeutic agents to cancer tissues (9,12,15,16). Using such methodology and the special prostate cancer model (7), we hypothesized that ligandreceptor pairs for targeting metastasizing androgen-independent prostate cancer cells could be identified.Here we select two novel ligand peptides that were selected in vivo from human androgen-independent prostate cancer xenografts. We show that they target the surface of an androgenindependent prostatic cell line in vitro and home to androgen receptor-null prostate tumors in vivo. With affinity chromatography, we next isolated their respective receptors, 78-kDa glucose-regulated protein (GRP78) and α-2-macroglobulin, from tumor lysates and as a proof of principle verified the peptide-GRP78 interaction in vitro with recombinant GRP78. These data confirm that GRP78 is a functional molecular target on prostatic cancer cell surfaces in vivo. Such ligand-receptor systems may be applicable to targeted therapy and should be...

show abstract

Association of extracellular matrix proteins fibulin‐1 and fibulin‐2 with fibronectin in bone marrow stroma

Cited by 30 publications

References 50 publications

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

Identification of Differentially Regulated Secretome Components During Skeletal Myogenesis

Cellular responses to ErbB-2 overexpression in human mammary luminal epithelial cells: comparison of mRNA and protein expression

Selection and identification of ligand peptides targeting a model of castrate-resistant osteogenic prostate cancer and their receptors

Contact Info

Product

Resources

About