Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro.

Abstract

Transforming growth factor type (3 (TGF-f3), when injected subcutaneously in newborn mice, causes formation of granulation tissue (induction of angiogenesis and activation offibroblasts to produce collagen) at the site of injection.These effects occur within 2-3 days at dose levels of <1 jg. Parallel in vitro studies show that TGF-(3 causes marked increase of either proline or leucine incorporation into collagen in either an NRK rat fibroblast cell line or early passage human dermal fibroblasts. Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) do not cause these same in vivo and in vitro effects; in both rat and human fibroblast cultures, EGF antagonizes the effects of TGF-(3 on collagen formation. We have obtained further data to support a role for

Five newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization

“…as an inhibitor of growth (Massague, 1990), on angiogenesis (Roberts et al, 1986), on immune responses (Wrann et al, 1987) and as an inhibitor of the induction of HLA-DR antigens by IFN-y (Darley et al, 1993). Our data indicate that, in common with many other neoplastic and normal cell types, oesophageal carcinoma cells produce TGF-,BI.…”

C-CAM1 expression: Differential effects on morphology, differentiation state and suppression of human PC-3 prostate carcinoma cells

“…Desmoplastic responses in tumors are often associated with oversecretion of TGF-b, a growth factor which in vivo stimulates recruitment and proliferation of stromal cells and inhibits the growth of epithelial cells, or with increased sensitivity to this growth factor (Lieberman and Lebovitz, 1990;Roberts et al, 1986). Thus, the presence of a pronounced desmoplastic response in nodules of PC3-11Csup+ cells raised the possibility that the suppression phenotype was associated with an increase in TGF-b or its receptors.…”

“…Among the C-CAM1 positive tumors, PC3-5Csup-( Figure 6B) demonstrated the highest degree of organization. While all of the C-CAM1 positive tumor nodules appeared to be well encapsulated, nodules formed by PC3-11Csup+ showed the most pronounced desmoplastic response (Roberts et al, 1986) that was manifested as a dense layer of connective tissue surrounding each small group of epithelial cells within the suppressed nodules ( Figure 6D). Ultrastructural analysis con®rmed the lower degree of histological organization in the PC3-11Csup+ nodules relative to PC3-Vsup-.…”

“…Because of the large desmoplastic response in the C-CAM1 positive tumors, particularly the PC3-11Csup+ nodules, and the known role of TGF-b in mediating such a response (Roberts et al, 1986) and in regulating growth of normal prostate epithelium (Barrack, 1997;Culig et al, 1996;Perry et al, 1997), levels of TGFb1, TGF-b2, TGF-b3, TGF-b receptor type I and TGF-b receptor type II were examined in vivo and in vitro to see if C-CAM1 expression was modulating this important growth regulatory pathway. As shown in Figure 12A, levels of TGF-b1 (transcript size=2.4 kb) and TGF-b3 (transcript size=3.8 kb) were very low in vitro for both the C-CAM1 positive and negative cell lines, while all the tumor nodules showed a consistent upregulation of these ligands.…”

Expression of a dominant negative type II TGF-β receptor in mouse skin results in an increase in carcinoma incidence and an acceleration of carcinoma development

“…Additionally, loss of TGF-b expression in benign skin papillomas is correlated with a high risk for malignant conversion (Missero et al, 1991;Glick et al, 1993;Cui et al, 1994;Glick et al, 1994). On the other hand, TGF-b can also stimulate malignant progression, possibly by its action on cell-matrix interaction, by its immunosuppressive activities or by enhancing angiogenesis (Roberts et al, 1986;Torre-Amione et al, 1990;Arrick et al, 1992;Glick et al, 1994;Cui et al, 1996). TGF-b conveys signals via two serine/threonine kinase receptors, type I and type II, both of which are necessary for signal transduction Derynck, 1994).…”