Disease relevance of FBLN1

• The interaction of fibulin-1 with fibrinogen. A potential role in hemostasis and thrombosis [1].
• Estradiol and fibulin-1 inhibit motility of human ovarian- and breast-cancer cells induced by fibronectin [2].
• By immunohistochemistry fibulin-1 was located in the stroma of several ovarian cancers and cysts [3].
• The findings highlight a potential role for fibulin-1 in the spread of ovarian cancer in the peritoneal cavity and/or in distal metastases [3].
• The fibulin-1 staining intensity in proximal stroma, close to the surface of epithelial cells and tumor cells, progressively increased from normal ovaries to serous carcinomas [4].

High impact information on FBLN1

• Therefore this protein, which we term fibulin, interacts with the fibronectin receptor in vitro and associates with the receptor in vivo [5].
• Fibulin, a novel protein that interacts with the fibronectin receptor beta subunit cytoplasmic domain [5].
• Fibulin is a potential mediator of interactions between adhesion receptors and the cytoskeleton [5].
• The same epitopes also participate in endostatin binding to heparan sulfate and sulfatides but not in its binding to the extracellular protein ligands fibulin-1 and fibulin-2 [6].
• Our results show that fibulin is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix when expressed by cultured cells or added exogenously to cell monolayers [7].

Biological context of FBLN1

• The gene coding for fibulin-1 (FBLN1) was located by in situ hybridization of 3H-labeled cDNA probes to human and mouse metaphase chromosomes [8].
• METHODS: Homozygosity mapping with 500 microsatellite markers spread over the whole genome (mean distance, 7.2 centimorgans [cM]) and mutation analysis of the complete coding region of FBLN1 [9].
• A mutation analysis of the complete coding region of FBLN1, which encodes interacting extracellular matrix proteins, revealed 4 previously undescribed single nucleotide polymorphisms [9].
• Heparin did not compete for the interaction between fibulin and FN, suggesting that the binding sites for fibulin and heparin are distinct [10].
• Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility [11].

Anatomical context of FBLN1

• Furthermore, such effects are cell-type specific, in that the migration of gingival fibroblasts and endothelial cells on FN substrata is not responsive to fibulin-1 [11].
• The effect of fibulin-1 was studied on the motility of the MDA-MB231 breast-cancer cell line, which does not express fibulin-1 [2].
• Fibulin-1 is an extracellular matrix (ECM) component of basement membranes and connective tissue elastic fibers, and a blood protein [12].
• Two transcripts of 2.4 and 2.7 kb are the predominant fibulin-1 mRNAs expressed in human tissues and cultured cells [12].
• Fibulin-1 was prominent in the matrix of the leptomeningeal anlage, in basement membranes of the neuroepithelium and the perineurium of peripheral nerves [13].

Associations of FBLN1 with chemical compounds

• Fibulin binds to itself and to the carboxyl-terminal heparin-binding region of fibronectin [10].
• Additional studies found that the mechanism for the motility-suppressive effects of fibulin-1 does not involve perturbations of interactions between alpha5beta1 or alpha4 integrins, or heparan sulfate proteoglycans with FN [11].
• Using a modified Boyden-chamber assay, we have evaluated the respective roles of estradiol and fibulin-1 on cell motility, one of the earlier steps of tumor invasion [2].
• Fibulin is a newly described extracellular matrix (ECM) glycoprotein whose function has not been elucidated [14].
• The amino-terminal portion of fibulin contains a repeated element with potential disulfide loop structure resembling that of the complement component anaphylatoxins C3a, C4a, and C5a as well as proteins of the albumin gene family [7].

Physical interactions of FBLN1

• We report here that the C-terminal domain confers on the full-length NOVH protein the capacity to bind fibulin 1C, a protein of the extracellular matrix that interacts with several other regulators of cell adhesion [15].

Regulatory relationships of FBLN1

• Fibulin-1 was found to inhibit haptotactic migration of MDA-MB231 cells to FN in a dose-dependent manner [2].
• The C-terminal domain of the regulatory protein NOVH is sufficient to promote interaction with fibulin 1C: a clue for a role of NOVH in cell-adhesion signaling [15].

Other interactions of FBLN1

• Evaluation of proteolytic fragments from all regions of FN allowed a fibulin-binding site to be localized within a 23-kDa heparin-binding fragment containing type III repeats 13-14 [10].
• The extracellular matrix proteins fibulin-1 and fibulin-2 in the early human embryo [13].
• These results set the stage for a study of NOVH-fibulin 1C interactions and their potential significance in cell-adhesion signaling in normal and pathological conditions [15].
• For this aim, MDA-MB-231 breast cancer cell line, which expresses both low basal levels of ERs and fibulin-1, was infected with recombinant ERalpha or ERbeta encoding adenovirus and treated with estradiol [16].
• Like human SHBG, fibulin-1 and fibulin-2 concentrate within the endometrial stroma [17].

Analytical, diagnostic and therapeutic context of FBLN1

• The binding of Fg to fibulin-1 was also observed in surface plasmon resonance assays, and a dissociation constant (Kd) of 2.9 +/- 1.6 microM was derived [1].
• In addition, it was found that fibulin-1 was able to incorporate into fibrin clots formed in vitro and was immunologically detected within newly formed fibrin-containing thrombi associated with human atherectomy specimens [1].
• In this report, ligand affinity chromatography and solid-phase binding analyses were performed to determine which ECM protein(s) interact with fibulin [10].
• In enzyme-linked immunosorbent assay, fibulin-1 bound to Fg (and fibrin) adsorbed onto microtiter well plastic, and conversely, Fg bound to fibulin-1-coated wells [1].
• Human fibulin-1D: molecular cloning, expression and similarity with S1-5 protein, a new member of the fibulin gene family [12].

References