Fibronectin

Fibronectin is found, in related forms, in serum as well as on the surface of normal, but not transformed cells. Addition of fibronectin to transformed cells causes a partial return to the normal phenotype in that it increases the adhesion of cells to other cells and to the substratum. It will also increase the saturation density achieved by 3T3 cells (Yamada et al., 1982). In contrast, antibodies to fibronectin will induce some of the characteristics of transformed cells in otherwise normal cells. 

Fibronectin is not present on mitotic cells and increases in amount on normal cells as they reach confluency or on cells arrested by low serum treatment ( 2.3 and 11.6) (Pearlstein, 1976 Hynes and Bye, 1974). 

Alitalo et al. (1980) showed that cultured human blood monocyte-derived macrophages secreted fibronectin, but did not deposit a pericellular fibronectin matrix as do various cormective tissue cell in culture. 

Ozone exposure (0.1 ppm for 10,20, or 30 min) to alveolar macrophages obtained by bronchoalveolar lavage from healthy, nonsmoking volunteers between the ages of 18 to 25 years, did not produce increased amounts of fibronectin (Devlin et aL 1994). 

In idiopathic pulmonary fibrosis, alveolar macrophages have glucocorticoid receptors, but glucocorticoid therapy does not suppress alveolar macrophage release of fibronectin (Lacronique et al. 

Fibronectin provides a mechanism for attaching the fibroblast to the connective tissue matrix and plays a role as a competence signal to move fibroblasts into the early portion of G, of the replication cycle (Erdogdu and Hasirci 1998). 

H2O2 alone induced no changes of fibronectin purified from human plasma, even at an 800-fold molar excess (Vissers and Winterbourn 1991). Radiolytic HO caused a rapid loss of tryprophan fluorescence, an increase in bityrosine fluorescence, and extensive crosslinking. 

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Rocco M, infusini E, Daga M G, Gogioso L and Cuniberti C 1987 Modeis of fibronectin EMBO J. 6 2343-9... 

Figure 13.19 Ribbon diagram of the stmcture of the extracellular domain of the human growth hormone. The hormone-binding region is formed by loops (yellow) at the hinge region between two fibronectin type III domains. (Adapted from J. Wells et al., Annu. Rev.

Figure 15.24 Ribbon diagram (a) and topology diagram (b) of the fibronectin type III domain, which is composed of a three-stranded and a four-stranded p sheet packed together as a compressed barrel.

Leahy, D.J., Hendrickson, W.A., Aukhil, A., Erickson, H.P. 5tructure of a fibronectin type II domain from tenascin phased by MAD analysis of the selenome-thionyl protein. Science 258 987-991, 1992. 

C, which is found in complement proteins FI, F2, and F3, first found in fibronectin I, the immunoglobulin superfamily domain N, found in some growth factor receptors E, a module homologous to the calcium-binding E-F hand domain and LB, a lectin module found in some cell surface proteins. (Adapted from Baron, M., Norman, D., and Campbell, I., 1991, Protein modnles. Trends in Biochemical Sciences 16 13—1 7.)... 

Protein lateral motion is much slower than that of lipids because proteins are larger than lipids. Also, some membrane proteins can diffuse freely through the membrane, whereas others are bound or anchored to other protein structures in the membrane. The diffusion constant for the membrane protein fibronectin is approximately 0.7 X 10 cmVsec, whereas that for rhodopsin is about 3 X 10 cmVsec. 

Cue D, Southern S, Southern P et al (2000) A non-peptide integrin antagonist can inhibit epithelial cell ingestion of streptococcus pyogenes by blocking a5 31 -fibronectin-Ml protein complexes. Proc Nat Acad Sci 97(6) 2858-2863... 

The leukocyte integrin a 4(3 1 (also known as VLA-4 and CD49d/CD29) is a cell adhesion receptor, which is predominantly expressed on lymphocytes, monocytes and eosinophils. VLA-4 is generally selective for the CS1 domain within fibronectin, with an essential requirement for LDV sequence for binding. VLA-4 also binds to VCAM-1 as a counter receptor. 

The integrin a 4(3 7 is restricted to leukocytes and can bind not only to VCAM1 and fibronectin, but also to MAdCAM the mucosal addressin or homing receptor, which contains immunoglobulin-like domains related to VCAM-1. 

Fibronectin receptor is a two-chain glycoprotein of the integrin family that serves as a transmembrane linker by binding to talin on the cytoplasmic side and to fibronectin on the external side of the membrane. The pull exerted by stress fibers on attached structures may be produced by bipolar assemblies of nonmuscle myosin molecules producing a sliding of actin filaments of opposite polarity. 

It is of interest that proteins termed motility factors (55-70 kD) are secreted by fetal cells and some tumor cells. These proteins act as autocrine factors and stimulate rapid movement by these cells. Motility factors induce the formation of cell processes that are packed with actin filaments and have an increased number of receptors for the matrix proteins laminin and fibronectin. The latter enhance the ability of the cells to bind to the extracellular matrix. Thus, it is likely that motility factors influence the organization of the cytoskeleton through changes taking place at the cell surface (reviewed by Warn and Dowrick, 1989). 

Edwards, J.G., Cambell, G., Carr, M Edwards, C.C. (1993). Shapes of cells spreading on fibronectin Measurement of the stellation of BHK21 cells induced by raising cyclic AMP, and of its reversal by erum and lysophosphatidic acid. J. Cell Sci. 104,399-407. 

Figure 4. Neurite outgrowth by LA-N-1 human neuroblastoma cells in culture. LA-N-1 human PNS neuroblastoma cells were grown for five days in N2 medium (as described by Bottenstein and Sato, 1979) on a polylysine and fibronectin-modified surface. The cells were plated in clumps, rather than as a single cell suspension, which enhances neurite extension. Very long processes result, and exhibit varicosities along their length. Most of the cells have migrated from the central clump. (Photo courtesy of Dr. jane Bottenstein.)...

F9 embryonal carcinoma cells have a simple set of growth supplements which are required for growth in serum-free medium insulin, transferrin, and fibronectin (Rizzino and Sato, 1978). Fibronectin is a component of the extracellular matrix and facilitates the attachment of the cells to the culture dish. In addition, high density lipoprotein (HDL) has been observed to promote the growth of F9 cells serum-free. 

Kim J. Han L Kim Y. et al. C-terminal heparin-binding domain of fibronectin regulates integrin-mediated cell spreading but not the activation of mitogen-activated protein kinase / / Biochem. J. 2001. V. 360. P. 239-245. 

Cornetta K, Croop J, Dropcho E, Abonour R, Kieran MW, Kreissman S, Reeves L, Erickson LC, Williams DA (2006) A pilot study of dose-intensified procarbazine, CCNU, vincristine for poor prognosis brain tumors utilizing fibronectin-assisted, retroviral-mediated modification of CD34-I- peripheral blood cells with 06-methylguanine DNA methyltransferase. Cancer Gene Ther 13 886-895... 

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