Fibulin-1 suppression of fibronectin-regulated cell adhesion and motility

Abstract

Fibulin-1 is an extracellular matrix protein often associated with fibronectin (FN) in vivo. In this study, the ability of fibulin-1 to modulate adhesion, spreading and motility-promoting activities of FN was investigated. Fibulin-1 was found to have pronounced inhibitory effects on the cell attachment and spreading promoted by FN. Fibulin-1 was also found to inhibit the motility of a variety of cell types on FN substrata. For example, the FN-dependent haptotactic motility of breast carcinoma (MDA MB231) cells, epidermal carcinoma (A431), melanoma (A375 SM), rat pulmonary aortic smooth muscle cells (PAC1) and Chinese hamster ovary (CHO) cells was inhibited by the presence of fibulin-1 bound to FN-coated Boyden chamber membranes. Cells transfected to overproduce fibulin-1 displayed reduced velocity, distance of movement and persistence time on FN substrata. Similarly, the incorporation of fibulin-1 into FN-containing type I collagen gels inhibited the invasion of endocardial cushion mesenchymal cells migrating from cultured embryonic heart explants. By contrast, incorporation of fibulin-1 into collagen gels lacking FN had no effect on the migration of endocardial cushion cells. These results suggest that the motility-suppressive effects of fibulin-1 might be FN specific. 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. Additional studies found that the mechanism for the motility-suppressive effects of fibulin-1 does not involve perturbations of interactions between α5β1 or α4 integrins, or heparan sulfate proteoglycans with FN. However, fibulin-1 was found to inhibit extracellular signal regulated kinase (ERK) activation and to suppress phosphorylation of myosin heavy chain. This ability to influence signal transduction cascades that modulate the actin-myosin motor complex might be the basis for the effects of fibulin-1 on adhesion and motility.

Cathepsin F and Fibulin-1 as novel diagnostic biomarkers for brain metastasis of non-small cell lung cancer

“…Studies have shown that FBLN1 can regulate cell morphology, adhesion, spread and promote cell movement, which is related to cancer growth, cell migration, and invasive growth [ 32 – 36 ]. The effect of FBLN1 as an ECM on cell migration and metastasis is complex [ 37 ]. On the one hand, the ECM is a storeroom of copious signal molecules, which can regulate various tumour-related pathological and physiological processes including tumour metastasis.…”

“…On the other hand, the composition and structure of the ECM determine the resistance and adhesion encountered by the migrating cells, thereby increasing the colonisation of tumour cells in the blood vessel wall and target organs [ 40 ]. The effect of FBLN1 on cell migration and metastasis is believed to be specific to cell and organ types [ 37 ]. Therefore, FBLN1 may be involved in regulating the various stages of BM of tumour cells, such as detachment from the primary tumour, infiltration of blood vessels, and colonisation of the brain parenchyma.…”

Quantitative Proteomic Approach for Discriminating Major Depressive Disorder and Bipolar Disorder by Multiple Reaction Monitoring-Mass Spectrometry

“…FBLN1 is an extracellular glycoprotein that is involved in cell adhesion and motility along fibers in the extracellular matrix. 79 The SNP located in FBLN1 has been associated with the hyperthymic temperament in a genome-wide association study (GWAS) of BD, 80 which is also a risk factor for BD itself.…”

Protein Ligands in the Secretome of CD36+ Fibroblasts Induce Growth Suppression in a Subset of Breast Cancer Cell Lines

“…Controls included the (i) neutralizing antibody for each of the corresponding recombinant proteins and (ii) colony formation assay for MCF10A. With respect to the concentration of recombinant proteins, we initiated with the published approximate ranges of SLIT3 [44] and FBLN1 [45,46] followed by serial dilution experiments of 0.1, 1, and 10 µg/mL for SLIT3 and FBLN1, and 0.1 and 1 µg/mL for PENK. SLIT3 and PENK at the concentration of 10 µg/mL and 1 µg/mL, respectively, induced growth suppression.…”