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Query: UMLS:C1519670 (tumor angiogenesis)
 6,052 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We review in this paper the role of heparin-binding growth factor (HBGF*) or fibroblast growth factor (FGF*), rat prostate cancer cells produce TGF-beta, IGF-II* and OGF*. Of these growth factors, TGF-beta and unknown labile factor with 19 kDa are the most probable candidates responsible for osteoblastic bony metastasis of prostate cancer. In vitro experiments suggest that TGF-beta modulates cell detachment of prostate cancer cells together with nutritional factors. HBGF-dependent growth of the prostate tumor epithelial cells is free from inhibition by TGF-beta, whereas normal prostate epithelial cells are sensitive to TGF-beta inhibition. Transfection experiments suggest that HBGF-2 (basic FGF) might be closely related to the malignant growth of prostate cancer, in addition to tumor angiogenesis.
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PMID:Potential role of HBGF (FGF) and TGF-beta on prostate growth. 149 11

Basic fibroblast growth factor is a protein widely distributed in the organism. It can stimulate the proliferation and differentiation of many cells and it is extremely potent in inducing angiogenesis, the formation of new blood vessels. In this article, some of its structural and biological properties are reviewed. In particular, the possible implications of basic fibroblast growth factor in normal and tumor angiogenesis are considered.
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PMID:Basic fibroblast growth factor and its relation to angiogenesis in normal and neoplastic tissue. 245 28

Tumor stroma formation results from the interaction of tumor cells and their products with the host and certain of its normal defense mechanisms, particularly the clotting and fibrinolytic systems. It is a process in which tumor cells render local venules and veins hyperpermeable with the result that fibrinogen and other proteins extravasate and clot, forming an extravascular crosslinked fibrin gel. Coagulation is mediated by an interaction between extravasated plasma clotting factors and tumor-associated and perhaps other tissue procoagulants. Parallel activation of the fibrinolytic system leads to substantial fibrin turnover, but fibrin nonetheless accumulates in amounts, variable from tumor to tumor, that are sufficient to provide a provisional stroma. This provisional stroma imposes on tumor cells a structure that persists even as tumor cells multiply and as the fibrin provisional stroma is replaced by mature connective tissue. The provisional fibrin stroma also serves to regulate the influx of macrophages, and perhaps other inflammatory cells, but at the same time, and in ways that are not fully understood, facilitates the inward migration of new blood vessels and fibroblasts, integral components of mature tumor stroma. Ascites tumors differ from solid tumors in that fibrin gel is not ordinarily deposited in body cavities and, as a result, there is no provisional stroma to impose an initial structure. Tumor stroma generation resembles the process of wound healing in many respects. However, it differs in the mechanism of its initiation, and in the apparent lack of a role for platelets. It also differs fundamentally in that invading tumor cells continually render new vessels hyperpermeable to plasma, thus perpetuating the cycle of extravascular fibrin deposition. In this sense, tumors behave as wounds that do not heal. Largely neglected in this review has been discussion of the numerous cytokines, mitogens, and growth factors that are widely believed to play important roles in tumor angiogenesis and wound healing; i.e., PDGF, FGF, EGF, TGF alpha, TGF beta, TNF, interferons, etc. This omission has been intentional, and for two reasons. First, these cytokines have already received considerable attention [100,123-128]. Second, it is not yet clear how closely the actions of these molecules, as described in vitro, relate to their functions in vivo. At present we are deluged with a surfeit of factors that have the capacity to induce new blood vessel formation in angiogenesis assays; these factors include not only peptides but lipids and even ions [126,129-131].(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. 246 81

The role of endothelial cell growth factors in the maintenance of the blood vessel wall is, as we have described here, much more complex than merely stimulating the mitogenesis of endothelial cells. The FGFs are capable of eliciting an array of responses in endothelial cells, some, or all, of which are important for neovascularization and the control of clot dissolution. These endothelial cell responses include protease elaboration, chemotaxis, and mitogenesis. That these growth factors seem neither to be constitutively released into the medium of cultured cells that synthesize bFGF, nor released into the bloodstream in vivo suggests that the temporal and local control of neovascularization may involve the regulation of growth factor release from cells such as endothelial cells, fibroblasts, and macrophages. Although there is no known example of this for bFGF, it is well known that both thrombin and Factor Xa stimulate the release of a mitogenic protein from endothelial cells and that low oxygen tension stimulates the release of macrophage-derived angiogenesis factor. In addition, both TGF beta and heparin alone appear to play a role in wound healing and vessel wall maintenance. The work of Roberts et al suggests that TGF beta is not only angiogenic, but also stimulates the growth of fibrotic tissue as well. Studies on mast cells demonstrated that released heparin is chemotactic for endothelial cells and can potentiate tumor angiogenesis. An attractive hypothesis is that these molecules not only act as FGF potentiators or inhibitors but that they also may exert their angiogenic effects by inducing FGF release from cells. Perhaps angiogenin, an angiogenic molecule with no mitogenic activity, works in this way. However, no evidence as yet exists concerning this point. A second level of control of neovascularization may involve the interaction of FGF with other molecules released into the same microenvironment. For example, thrombin and TGF beta released from platelets, as well as heparin released from mast cells, have all been demonstrated to affect bFGF activity in vitro and may act as modifiers of FGF activity in vivo. Since bFGF can modulate fibrinolytic activity, one could imagine that its release into a wound region of the vasculature could have detrimental effects on clot formation and subsequent wound healing. Thus, the transient inhibition of bFGF activity by TGF beta would allow clot formation before the induction of neovascularization by bFGF, TGF beta thereby playing a role in the regulation of the sequence in which events occur.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endothelial cell growth factors and the vessel wall. 332 39

In the preceding sections we have shown evidence that growth-promoting factors are involved in three basic situations. In normal embryonic development and function of mature organisms, growth factors such as NGF and EGF are of prime importance in supporting the necessary embryonic cell proliferation and the development of specific cell types. Other factors operate on subsets of mature cells during specialized functions such as inflammation. Included in this set would be factors such as CSF/MGF and Interleukin-2. Another basic function of growth factors has been shown to be wound repair and organ regeneration. This includes the well characterized PDGF and FGF as well as the various renotropic factors and liver growth factors. As these factors must operate in mature organisms with many different cell types and similar cell types in many locations, more specificity is needed than in embryonic growth. This has resulted in the organ specific factors such as the renotropins and in the unique delivery system of the PDGF. The recent discovery and characterization of the transforming growth factors has provided a possible connection between embryonic and normal developmental growth and the rapid cellular proliferation characteristic of tumor cells. The TGF not only interacts with receptors for normal growth factors such as EGF but are also detectable in low levels in normal tissue and embryos. The exact relationships between these various factors will have to await the determinations of more amino acid sequences for comparisons. The other tumor-related product, tumor angiogenesis factor, is also found in normal tissue and inflammatory reaction sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of polypeptide growth factors in normal and abnormal growth. 640 May 65

Epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha) stimulated cell migration, chemotaxis, and the expression of tissue-type plasminogen activator (t-PA) in human omental microvascular endothelial (HOME) cells. Hepatocyte growth factor (HGF) stimulated cell proliferation, but had a negligible stimulatory effect on cell migration, the expression of t-PA and tube-like formation into collagen gel in HOME cells. Basic fibroblast growth factor stimulated cell proliferation, cell migration, tubulogenesis and the expression of urokinase-type plasminogen activator (u-PA) in bovine aortic endothelial (BAE) cells. HOME and BAE cells had both high- and low-affinity receptors for HGF. In BAE cells, u-PA activity and tube-like structures in collagen gel were induced in the presence of HGF alone. In contrast, in HOME cells, t-PA activity and tube-like structures were induced in the presence of TGF-alpha alone, but not in the presence of HGF alone. However, we observed a marked induction of tube formation by HOME cells when both t-PA and HGF were added simultaneously. In the model system for tumor angiogenesis, when HOME cells were co-cultured with a renal cancer cell line, KPK13, tube-like structures were induced in the presence of HGF:KPK13 cells expressed large amounts of t-PA mRNA. Our present study suggested that HGF in concert with active t-PA could be angiogenic in HOME cells.
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PMID:Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells. 750 7

Basic fibroblast growth factor (bFGF) is a heparin-binding protein, expressing potent mitogenic and angiogenic properties. Elevated levels of bFGF have been identified in human gliomas and glioma cell lines, suggesting that bFGF expression is involved in the aberrant growth patterns associated with these tumors. In the present study, the influence of bFGF on additional parameters of glioma cell malignancy was evaluated utilizing three distinct methods to suppress bFGF expression or activity including antisense oligonucleotide primers, a neutralizing monoclonal antibody or an inhibitor of the agonist action of bFGF: (1) The addition of 30 microM bFGF-specific antisense oligonucleotide primer to the human glioma cell line SNB-19 resulted in a 55% inhibition in colony formation in soft agar. This effect was dose-dependent and specific, as sense strand primer was ineffective in suppressing growth. In addition to exhibiting fewer colonies, antisense treatment significantly altered colony morphology. (2) SNB-19 cell growth in culture was suppressed in the presence of a neutralizing bFGF-specific monoclonal antibody. (3) Inositolhexakisphosphate, a newly identified antagonist of FGF binding and activity, suppressed SNB-19 cell growth in soft agar culture. These results demonstrate that bFGF may regulate glioma growth and progression independent of its role in tumor angiogenesis and that bFGF release or secretion may be required for these actions.
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PMID:Basic fibroblast growth factor expression is required for clonogenic growth of human glioma cells. 847 85

Basic fibroblast growth factor (bFGF) is an established growth factor for melanocytes and a potent angiogenic factor. The expression of bFGF was investigated in 23 desmoplastic melanomas. (DM) (12 males, median age 64 years, and 11 females, median age 54 years) by immunostaining of formalin-fixed, paraffin-embedded sections with high-affinity purified antibody raised against recombinant human bFGF (Scios Nova, Inc.). The tumors were characterized by level II invasion in 1 case (5%), level IV invasion in 11 cases (48%), level V invasion in 8 cases (35%), and indeterminate in 3 cases. bFGF expression was observed in 22 of 23 tumors (95%), either immune localized to tumor cell nuclei in 17 of 22 tumors (77%), or to the cytoplasm of tumor cells in 5 of 22 tumors (23%). Also in these cases, bFGF was strongly expressed in the nuclei of vascular endothelial cells. Maximal expression was noted in the peripheral blood vessels of 20 tumors (91%) versus intratumoral vessels of 13 DM (59%). In conclusion, the expression of predominantly nuclear bFGF by tumor cells in DM suggests a role in mediating the desmoplastic phenotype. In addition, the localization of bFGF to vascular endothelium, particularly at the periphery of the tumor, may be relevant to tumor angiogenesis.
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PMID:Expression of basic fibroblast growth factor in desmoplastic melanoma. 872 45

Several groups have shown that quantitation of tumor angiogenesis by counting blood vessels in primary breast cancer gives an independent assessment of prognosis. Poor prognosis is associated with high blood vessel counts. We have shown that the rate of cell division in endothelial cells is much higher in breast tumours than in normal breast. Breast cancer cell lines and primary human breast tumours express a wide range of vascular growth factors, including VEGF, placenta growth factor, pleiotrophin, TGF beta 1, acidic and basic FGF, and platelet-derived endothelial cell growth factor. Inhibiting angiogenesis by blocking vascular growth factors would be difficult with highly specific agents, but drugs with a broader spectrum of antagonism may be effective. We have developed several suramin analogues which are less toxic than suramin in vivo but more potent in inhibiting angiogenesis, and these have been developed for Phase I. A combination of anti-angiogenesis agents with drugs activated by hypoxia may also be useful, because anti-angiogenesis alone may not kill cells, whereas activation of hypoxic drugs could synergize. New endpoints may be necessary because inhibition of new blood vessel formation may not cause tumour regression. Thus, the endpoint of stable disease and biochemical assessment of inhibition of angiogenesis may be much more important in therapeutic studies and for drug development in the future. The prognostic importance of angiogenesis suggests that this should be a major new therapeutic target.
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PMID:Breast cancer angiogenesis--new approaches to therapy via antiangiogenesis, hypoxic activated drugs, and vascular targeting. 882 27

Basic fibroblast growth factor (bFGF) is a potent endothelial cell growth factor that does not normally circulate in healthy nonpregnant adults. bFGF has been reported in plasma from patients with certain tumors consistent with a postulated role in tumor angiogenesis. In the present study we used an endothelial cell bioassay to test for a bFGF-like substance in plasma and urine from patients with noninsulin-dependent diabetes mellitus. We found increased bFGF immunoreactivity that correlated with bFGF-like endothelial cell growth-promoting activity in plasma from a subset of diabetic patients with persistent microalbuminuria or overt proteinuria. Plasma (bFGF-like) growth-promoting activity was significantly correlated with glycosylated hemoglobin (P < 0.05), but not patient age, race, degree of proteinuria, or systolic blood pressure. In a group of microalbuminuric or proteinuric diabetic subjects well matched according to baseline clinical characteristics, plasma (bFGF-like) growth-promoting activity was significantly decreased (P < 0.0001) in the subgroup of patients who were being treated with an angiotensin-converting enzyme inhibitor simultaneous to blood drawing for plasma growth assay. In patients not treated with an angiotensin-converting enzyme inhibitor, multiple regression analysis showed that retinopathy was the only variable significantly associated with plasma growth-promoting activity. These results imply that plasma bFGF endothelial cell growth-promoting activity is increased and may contribute to pathophysiology in a heterogeneous subset of noninsulin-dependent diabetes mellitus patients with persistent microalbuminuria or overt proteinuria.
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PMID:Increased basic fibroblast growth factor-like substance in plasma from a subset of middle-aged or elderly male diabetic patients with microalbuminuria or proteinuria. 895 57


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