Transforming growth factor-beta stimulates the expression of fibronectin and collagen and their incorporation into the extracellular matrix.

We have identified a cell type in 7-day-old rat optic nerve that differentiates into a fibrous astrocyte if cultured in the presence of fetal calf serum and into an oligodendrocyte if cultured in the absence of serum. In certain culture conditions some of these cells acquire a mixed phenotype, displaying properties of both astrocytes and oligodendrocytes. These observations suggest that fibrous astrocytes and oligodendrocytes develop from a common progenitor cell and provide a striking example of developmental plasticity and environmental influence in the differentiation of CNS glial cells.

A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium

How does the extracellular matrix direct gene expression

A recently characterised class of adhesive, high molecular weight glycoproteins is present on the surfaces of cells, in connective tissue matrices, and in extracellular fluids. These proteins may have important roles in cellular adhesion, malignant transformation, reticuloendothelial system function, and embryonic differentiation.

Fibronectins—adhesive glycoproteins of cell surface and blood

It has long been appreciated that, for many types of cells, attachment to a substrate is required for their replication. Collagen substrates enhance the growth (64, 70, 109, 238) as well as the differentiation (40, 69, 85, 86, 146, 161, 184), of many cells in culture above that observed with other substrates such as plastic and glass. As discussed in this report, many cultured cells including fibroblasts, myoblasts, hepatocytes, chondrocytes, and certain epithelial cells are thought not to bind directly to the collagen substrate or to the plastic surface of culture dishes (31, 73, 74, 76, 77, 89, 93, 113, 164, 220) . Instead, extracellular glycoproteins bind the cells to the substrate. One of these attachment proteins, fibronectin, has been extensively studied (99, 151, 166, 227, 228, 244) . Fibronectin is produced by fibroblasts (13, 197, 246) and endothelial cells (102, 140) as well as some other cell types . It is also present in high concentrations in blood and serum (152) . In culture, serum fibronectin, as well as that produced by the cells, can bind to both the collagen substrates and the tissue culture plastic surface and mediate the attachment of cells (73, 113, 164, 242) . Circulating fibronectin participates in a variety of reactions important to wound healing, including the adhesion and spreading of platelets on collagen (10, 14, 75, 100, 204), binding to the fibrin clot (74, 150, 198) and to collagen (37, 46, 94, 103, 119), promoting opsonization reactions by phagocytic cells (18, 94, 201), and promoting fibroblast migration (6, 61) . Thus, fibronectin not only functions as an attachment protein, but also may play an important role in repair reactions . In the case of certain differentiated cells, such as chondrocytes (89) and epithelial cells (159, 220), glycoproteins different from fibronectin are active in attachment. The components of these extracellular matrices of fibroblasts, chondrocytes, and epithelial cells differ with the cell type, and they require separate attachment proteins to provide additional specificity to the interaction ofthe cell with its matrix. Alterations in cellsubstratum interactions are observed in differentiating cells and after spontaneous transformation of cells or exposure to oncogenic agents (99, 228) . This review will briefly outline our current knowledge of the types of collagen and their distribution and biosynthesis. Then, the interaction of cells with colREVIEW

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Role of collagenous matrices in the adhesion and growth of cells.

Fibronectin, a plasma protein immunologically identical with a major surface protein of normal fibroblasts, was found to bind to collagen and gelatin. A solid phase enzyme immunoassay was used for the binding tests. Collagen, gelatin or various control proteins were adsorbed to a plastic surface. Binding of fibronectin was detected using purified fibronectin antibodies conjugated to alkaline phosphatase. Circulating fibronectin and fibronectin obtained from fibroblast cultures both showed specific binding to collagen and gelatin. Preparative affinity chromatography of plasma on gelatin coupled to Sepharose gave electrophoretically and immunologically pure fibronectin in high yields. Malignantly transformed fibroblasts lack surface fibronectin. Our findings suggest the possibility that this results in a lack of anchorage to the surrounding intercellular matrix, which could contribute to the malignant growth behavior.

Binding of soluble form of fibroblast surface protein, fibronectin, to collagen.

Interaction of fibronectin with antibodies and collagen in radioimmunoassay

Human AFP purified from fetal serum and amniotic fluid was separated into three different variants by chromatography on concanavalin A insolubilized on Sepharose (Con A--Sepharose). The three variants were indistinguishable in immunodiffusion and radioimmunoassay. Sera from patients with yolk-sac tumor and amniotic fluid from early pregnancy were found to contain a high proportion (15-45%) of AFP which does not bind to Con A, while AFP in fetal and newborn sera, and in amniotic fluid from late pregnancy, contained less (2-6%) of this variant. The use of a large excess of Con A--Sepharose and the fact that the non-bound AFP consistently eluted as non-bound in rechromatography showed that this AFP is non-reactive with Con A. Fractionation of radiolabelled AFP from cord serum in a mixture with amniotic fluid verified the difference in the amount of the Con-A nonreactive variant in AFP from these two sources. These results suggest that AFP synthesized by the yolk-sac tissue and by the liver are glycosylated differently. The variant may prove to be diagnostically useful.

Developmental changes in carbohydrate moiety of human alpha-fetoprotein

Fibronectin (also called SFA,'.' LETS galactoprotein a,5 CSP,(' Z p r ~ t e i n , ~ C l g , ' CA F.9 and C A P \" . \" ) , a cell surface and plasma protein,'i2 has many interesting biologic properties, such as nonexistence in surfaces of transformed ce~~s4 .s .7 .12-14 and interaction with fibrin15 and collagen.'6 Thesc properties have made it the subject o f m u c h current research. It still remains a protein in search of a function, especially in regard to its plasma form, but the evidence available suggests that it may function in the attachment of cells t o the extracellular matrix.'.'' I n this paper, we will briefly summarize some of our past work and present some new data on the immunochemical properties and detection of fibroncctin and its interaction with structural proteins, such a s collagen and fibrin.

Immunochemical and collagen-binding properties of fibronectin*

Pregnancy-specific beta-1-glycoprotein (PSBG) and human chorionic gonagotrophin (hCG) were measured by specific radioimmunoassays in 73 serum samples from eight patients treated for gestational choriocarcinoma. Both markers were initially present in all cases, but at the time of writing both had levelled off in six cases and decreased markedly in two. Usually hCG was detectable for longer than PSBG during the course of chemotherapy. Both PSBG and hCG reappeared on clinical recurrence. However, at times during the follow-up period one trophoblastic marker only was expressed. This was hCG in most cases, but in one case PSBG alone was encountered. These results suggest that PSBG may serve as an additional marker for the detection of residual tumour growth in patients with trophoblastic tumours.

Eva Engvall

Papers

Binding of soluble form of fibroblast surface protein, fibronectin, to collagen.

Interaction of fibronectin with antibodies and collagen in radioimmunoassay

Developmental changes in carbohydrate moiety of human alpha-fetoprotein

Immunochemical and collagen-binding properties of fibronectin*

Detection of trophoblastic tumour activity by pregnancy-specific beta-1-glycoprotein.