Showing papers on "Angiogenesis published in 1980"

Angiogenesis in vitro

Abstract: Cloned capillary endothelial cells, cultured in tumour-conditioned medium, form capillary tubes. By light and electron microscopy these tubes resemble capillaries in vivo. This first demonstration of angiogenesis in vitro: (1) shows that all the information necessary to develop an entire capillary network in vitro is expressed by one cell type; (2) suggests a mechanism for lumen formation; and (3) offers a possibility of distinguishing between direct and indirect angiogenesis factors.

Mast cell heparin stimulates migration of capillary endothelial cells in vitro

Abstract: Migration of capillary endothelial cells is an important component of angiogenesis in vivo. Increased numbers of mast cells have been associated with several types of angiogenesis. We have used a quantitative assay in vitro to demonstrate that mast cells release a factor that significantly increases bovine capillary endothelial cell migration. The factor is present in medium conditioned by mast cells as well as lysates of mast cells. The stimulatory effect of mast cells on migration is specific for capillary endothelial cells. Furthermore, mast cells have no mitogenic activity for capillary endothelial cells. Of all the secretory products of mast cells tested, only heparin stimulated capillary endothelial cell migration in vitro. Heparin preparations from a variety of sources stimulated capillary endothelial cell migration to the same degree but did not stimulate migration of several other cell types. The migration activity of heparin and mast cell conditioned medium was blocked by specific antagonists of heparin (protamine and heparinase), but not by chondroitinase ABC. The migration activity of mast cell conditioned medium was resistant to heat (100 degrees C) and incubation with proteolytic enzymes. These results suggest that the role of mast cells in angiogenesis may be to enhance migration of the endothelial cells of growing capillaries.

Migration of capillary endothelial cells is stimulated by tumour-derived factors.

Abstract: Angiogenesis, the growth of new blood vessels, occurs normally during osteogenesis, luteinisation and the development of the embryo, and in pathological states such as chronic inflammation, certain immune reactions and neoplasia1. Furthermore, solid tumours have been reported to secrete a diffusible factor which promotes the directional growth of new capillaries towards a growing tumour2. Two events required for the formation of a new capillary in response to an angiogenesis factor in vivo are the migration and subsequent proliferation of capillary endothelial cells3. Progress in purifying angiogenesis factors and studying their action has been hindered, however, by the lack of quantitative in vitro assays for capillary cell migration and proliferation. Recently, we have been able to isolate clonal cell lines of bovine capillary endothelial cells that can be maintained in long-term culture using tumour-conditioned growth medium4. I now report a quantitative in vitro assay for endothelial cell migration based on the phagokinetic track assay of Albrecht-Buehler5. The evidence presented here demonstrates that tumour-derived factors stimulate the migration of capillary endothelial cells whereas the same factors have no effect on the migration of aortic endothelial cells.

Control of tumor growth in animals by infusion of an angiogenesis inhibitor

Abstract: Angiogenesis and tumor growth were inhibited in two different animal models by regional infusion of a partially purified cartilage extract. In rabbits bearing corneal implants of V2 carcinoma and receiving the inhibitor, vascular growth rates were < 3% of those in control animals receiving either Ringer's solution or bovine trypsin inhibitor (Trasylol). Subconjunctival B16 melanoma implants in mice receiving the inhibitor weight < 2.5% of implants in mice receiving Ringer's solution, Trasylol, or albumin. Histologic study of major organs and standard blood tests revealed no toxic effects in any of the animals. The inhibitor did not retard the growth of either tumor cell type in tissue culture at concentrations as high as 1 mg/ml. These results suggest that the cartilage factor does not interfere with the growth of the tumor cell population directly but that it prevents tumor growth by inhibiting angiogenesis.

Adult tissues contain chemo-attractants for vascular endothelial cells

Abstract: New blood vessel formation, or angiogenesis, occurs through the migration of endothelial cells in elongated sprouts. These sprouts are directed preferentially towards the inciting stimulus1–3. Several studies have demonstrated that certain chemical substances can stimulate angiogenesis4–7. In these cases, endothelial cell migration towards the chemical stimulus may be due to a preferential migration of cells from lower to higher concentrations of the mediator. Such concentration gradient-dependent cellular migration has been termed chemotaxis8. Using a modification of the Boyden chamber technique9 to measure chemotaxis in vitro, we have now found that extracts of various adult bovine tissues have potent chemotactic activity for vascular endothelial cells. Adult bovine serum lacks similar chemotactic activity.

Angiogenesis by capillary endothelial cells in culture.

Abstract: Capillary endothelial cells cloned from bovine and human tissues were grown in long-term culture In the presence of tumor-conditioned medium, capillary tubes formed when the cells became confluent Each tube began as a longitudinal vacuole in one cell and then appeared to be extruded and connected from one cell to the next Branches appeared, and a capillary network developed over a period of 2 to 3 weeks By light and electron microscopy, the tubes were nearly identical to capillaries in vivo These experiments: (1) Demonstrate angiogenesis in vitro; (2) Show that all the information necessary to develop an entire capillary in vitro can be expressed by one cell type; (3) Suggest a mechanism for lumen formation by capillaries in vivo; (4) Offer a possibility of distinguishing between direct and indirect angiogenesis factors

Mechanism of the induction of angiogenesis by human neoplastic lymphoid tissue: studies on the chorioallantoic membrane (CAM) of the chick embryo.

Abstract: The angiogenic activity of various neoplastic and control tissues, cells and extracts has been tested on the chorioallantoic membrane of the chick (CAM). The vascular response was assessed macroscopically and also by histological examination. Angiogenesis was induced by a number of neoplastic implants the most potent being derived from Hodgkin's disease, histiocytic lymphoma or glioma tissue. Boiled tumour tissue was ineffective. Lymphocytes extracted from human lymphomas, activated normal peripheral blood lymphocytes and established lymphoid cell lines of neoplastic origin were generally effective in inducing neovascularisation through millipore membranes as were 90,000-100,000 MW fractions of human tumour tissue. In all cases examined histologically a mononuclear cell infiltrate in the CAM mesoderm accompanied a positive vascular response. These results implicate host monocytes in the generation of neovascularisation by neoplastic tissue.

Weibel-Palade Bodies in Endothelial Cells as a Marker for Angiogenesis in Brain Tumors

Abstract: A transmission electron microscope study was made of eight childhood brain tumors divided up into three zones, center, edge, infiltrating zone, and also of adjacent "normal-looking" brain. In seven of eight tumors, the numbers of Weibel-Palade bodies in endothelial cells were significantly increased in peripheral zones compared with central zones. A similar significant increase was observed after treatment of chick chorioallantoic membranes with tumor angiogenesis factor. It is suggested that large numbers of Weibel-Palade bodies may be a marker for proliferating endothelial cells in vivo.

Cellular and molecular mechanisms in angiogenesis.

Abstract: Low concentrations of copper sulphate, Dispirin, or Walker carcinoma extract elicit intraocular vascularization when tested by anterior chamber implants in rats. The response is markedly depressed by pre-treatment of animals with methylprednisolone acetate, suggesting that such induced vascularization is mediated by leucocytes. Since many agents inducing vascularization also induce migration of cultured endothelial cells, it raises the problem of how to isolate and study the action of possible leucocyte-derived angiogenic factors. Regardless of the identity of the natural angiogenic factor or factors, it is proposed that during blood vessel formation specialized endothelial cells migrate in response to an angiogenic signal and deposit fibronectin on which other cells can track and subsequently adhere, forming an endothelium.

Mechanism of the induction of angiogenesis by human neoplastic lymphoid tissue: studies employing bovine aortic endothelial cells in vitro.

Abstract: Extracts of human neoplastic tissue (three Hodgkin's lymphomas; three gliomas and one liposarcoma) previously shown to induce angiogenesis in vivo did not stimulate the proliferation of bovine aortic endothelial cell monolayers when tested in vitro. Proliferation was induced by coculture of endothelial cells with human or animal macrophages or with supernatants derived from these cells. However, angiogenic extracts were chemotactic both for guinea pig peritoneal macrophages and human mononuclear cells in vitro. These results imply that tumour extracts act indirectly to induce angiogenesis in vivo via their effect on host macrophages.

[Effects of anticancerous agents on the microvascular system of experimental malignant tumors (author's transl)].

Abstract: Walker 256 carcinosarcomas were transplanted under the skin and in the bone marrow of the femur of Wistar rats to investigate the tumor angiogenesis and effect of anticancerous agents on it. Microangiography was performed on tumors in different stages after transplantation and on treated tumors in different stages after a single shot of Adriacin or Endoxan into the intraperitoneum. The tumors were histologically examined. The results were as follows: 1. Angiogenesis was found at the host side near the tumor in the beginning of the subcutaneous transplantation and formation of vascaular network was seen at the peripheral area in the tumor after 5-7 days. No blood vessel was found at the central region of the tumor, and so-called "sinusoidal lake" was seen at the border zone of central and peripheral regions, suggesting the impending central necrosis. The vascular network became loose and blood vessels became of larger diameters and sinusoidal blood vessels were found afater about 14 days. In the case of intramedullary transplantation, blood flow stopped in the marrow already after about 10 days and rich network of blood vessels was observed in the spicula. 2. In the Adriacin group, only a weak inhibitory effect on tumor growh was found. There was no degeneration of tumor cells, but a little disorder of tumor cell cords. The effects of the drug on the capillaries were remarkable. The diameter of the capillary was narrowed, with fragmented vascularity and disappearance of capillary network. It was estimated that effective amount of the drug might not reach tumor cells because of circulatory disturbance due to obstruction of the capillaries caused by Adriacin. 3. In the Endoxan group, inhibitory effect of the drug was remarkable, and degeneration and transformation into giant cells of tumor cells, with a decrease of tumor cells and proliferation of interstitial connective tissues. The microvascular system maintained its network structure for rather a long period and the network was reduced with an increase of the connective tissue, but no fragmentation was found. It was suggested that sufficient Endoxan might have reached the tumor cells and cause their degeneration and destruction, followed by decrease of tumor angiogenesis factor (TAF) and by secondary reduction and disappearance of the microvascular system.