Eosinophil Interactions with Extracellular Matrix Proteins
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
Other ECM proteins include the collagens, which are a highly specialized glycoprotein family with a least 16 distinct members that are thought to be encoded by at least 30 genes (9). Collagens are very widespread, being found in the stroma, basement membranes, cartilage, tumors, skin, tendons, and, in the case of asthma, the thickened layer of connective tissue found below the epithelium (primarily collagen type IV). Vitronectin has been identified in both the ECM and plasma, the latter being found as either a single or two-chain form held together by disulfide bridges. The form found in tissues is not yet known. Vitronectin is encoded by a single gene and has a variety of functions, being involved in phagocytosis, tissue repair, and immune function. Cellular attachment to vitronectin is mediated by αvβ3, αIIbβ3, and αvβ5 via an RGD sequence (33).
Dermal Fibroblast Function
Brian J. Nickoloff in Dermal Immune System, 2019
The composition of the surface on which fibroblasts are grown determines the degree to which they adhere to that surface. Fibroblasts adhere, spread, and develop focal adhesions better on surfaces coated with extracellular matrix proteins such as fibronectin or vitronectin, and adhere poorly and do not develop focal adhesions when they are plated on glass in serum-free medium or medium supplemented only with bovine serum albumin.75 Serum-spreading factor (vitronectin) is probably the major extracellular component of focal adhesions when cells are grown in serum-containing medium.73,76 Vitronectin, like fibronectin, has a heparin-binding domain and an Arg-Gly-Asp (RGD) sequence that is also common to other matrix proteins that interact with cells.73,77 Both the heparin-binding domain and the RGD sequence are necessary for formation of focal adhesions by cells.73,78
Tissue Engineering of Articular Cartilage
Kyriacos A. Athanasiou, Eric M. Darling, Grayson D. DuRaine, Jerry C. Hu, A. Hari Reddi in Articular Cartilage, 2017
Vitronectin is another protein that has been investigated as a scaffold coating for tissue engineering. Past results showed that vitronectin controls osteoblast attachment and spreading, as opposed to a more abundant protein like fibronectin, when used as a coating in vitro (Thomas et al. 1997). While these findings are not directly applicable to chondrocytes, vitronectin could still be important in modulating the attachment of cells in osteochondral constructs. Other experimental studies investigating vitronectin have shown that it competes better than most proteins when adsorbing to surfaces in the presence of serum (Wyre and Downes 2002). Adhesion of chondrocytes to vitronectin may be through the α5β1, αVβ5, and αVβ3 integrins.
Understanding collagen interactions and their targeted regulation by novel drugs
Published in Expert Opinion on Drug Discovery, 2021
Marialucia Gallorini, Simone Carradori
Vitronectin (VN) is a multifunctional glycoprotein which binds to different biological ligands and, by binding to different types of integrins, mostly via the RGD sequence, plays a key role in tissue remodeling by controlling cell adhesion. In addition to that, VN owns two domains for collagen-binding and interacts with collagens I, II, III, IV, V and VI. As for fibronectin (FN), its interactions with collagen are crucial during the genesis of fibrils. Fibronectin has also been discovered as a target protein for the diagnosis of high-risk micro-metastasis of breast cancer. A successful approach to prevent metastatic invasion could be the selective delivery of therapeutic drugs to highly fibronectin-expressing metastatic tumor sites [93]. Finally, the crosstalk between collagens and non-collagenous bone proteins, such as bone sialoprotein II (BSPII) and osteonectin (SPARC, secreted protein acidic and rich in cysteine), is involved in tissue remodeling and cancer-related metastases. The SPARC protein has furthermore been identified as a potential therapeutic target to prevent breast cancer bone metastasis [94].
Mass spectrometry analysis of glycoprotein biomarkers in human blood of hepatocellular carcinoma
Published in Expert Review of Proteomics, 2019
Kwang Hoe Kim, Jin Young Kim, Jong Shin Yoo
Vitronectin (VTN) is a well-characterized HCC-related protein. Yoo and coworkers developed an MRM MS technique to detect a tryptic peptide derived from VTN [95]. They found that abnormal N-glycosylation affects the efficiency of tryptic digestion due to steric hindrance. As a results, the plasma level of the tryptic peptide differed between the patients with HCC and the healthy subjects. The AUROC value of the tryptic peptide from VTN was 0.978, with a sensitivity of 88.9% and specificity of 100% (Table 1). Also, The AUROC value of the deglycosylated tryptic peptide from afamin (AFM) was 0.723 (sensitivity of 78.6% and specificity of 75.0%). This LC-MS/MS method enables the discovery and validation of candidate protein biomarkers in serum or plasma without the need for complex or antibody-based enrichment [95].
Anti-integrin therapy for retinovascular diseases
Published in Expert Opinion on Investigational Drugs, 2020
Ashay D. Bhatwadekar, Viral Kansara, Qianyi Luo, Thomas Ciulla
SF-0166 (SciFluor Life Science, MA, USA) is a small molecule inhibitor of integrin αvβ3. Due to its optimized physicochemical properties, SF-0166 can distribute to the posterior segment of the eye after topical administration, and the drug concentration was maintained for more than 12 hours [64]. In in vitro studies, SF-0166 was shown to inhibit cell adhesion to vitronectin across a variety of cell lines of rat, rabbit, dog origin, and shown to inhibit integrin-ligand interactions for the human dermal microvascular endothelial cells. In addition to αvβ3, SF-0166 also inhibits integrins αvβ6, and αvβ8 at nanomolar concentrations; however, it does not inhibit binding to αvβ5 or fibronectin via α5β1 integrins [64]. SF-0166 was found to inhibit neovascularization in the oxygen-induced retinopathy mouse model after topical administration. In the laser-induced CNV animal model, SF-0166 decreased lesion area; this decrease was comparable to bevacizumab. In the rabbit model of VEGF-induced vascular leakage model, topically delivered SF-0166 exhibited a dose-dependent reduction in vascular leakage [64].
Related Knowledge Centers
- Bone
- Cell Adhesion
- Integrin
- Glycoprotein
- Extracellular Matrix
- Complement System
- Hemopexin Family
- Gene
- Alpha-V Beta-3
- Serpin