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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A malignant cell population needs the development of microvessels in order to grow and metastasize. Recently, a role for the p53 gene in the regulation of this angiogenic process has been suggested. Wild-type p53 is involved in the secretion of Trombospondin-1 (TSP-1), an angiogenesis inhibitor. Mutations of the p53 gene cause a downregulation of TSP-1 mRNA in cell lines. Mutant p53 also upregulates the expression of vascular endothelial cell growth factor, a potent angiogenic factor. Together with the reported association of p53 protein overexpression and microvessel density (MVD) in head-and-neck squamous-cell carcinoma, these in vitro findings led us to investigate whether this association would also apply in colorectal adenocarcinomas. Structural changes of the p53 gene are the most frequent observed mutations in colorectal carcinoma and are suspected to be involved in the carcinogenesis at a relatively early stage. Parallel tissue sections from primary colorectal adenocarcinomas were immunostained for CD31, an endothelial cell marker, and with DO7, recognizing both mutant and wild-type p53 protein overexpression. The presence of p53 protein overexpression was found to be significantly associated with high MVD in the vascular hot spots. Our results are in accordance with the in vitro studies on the involvement of p53 in angiogenesis. Mutant p53 might stimulate tumor angiogenesis both indirectly, by augmenting the tumor cell proliferation, and directly, by upregulating angiogenic factors and downregulating angiogenic inhibitors.
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PMID:Correlation of intratumoral microvessel density and p53 protein overexpression in human colorectal adenocarcinoma. 877 72

There is considerable evidence that vascular endothelial growth factor is involved in the vascularization and growth of primary tumors and in the formation of metastases. The expression of vascular endothelial growth factor depends on activated oncogenes and inactivated tumor-suppressor genes as well as several other factors, e.g., growth factors, hypoxia, and tumor promoters. Substantial expression of vascular endothelial growth factor receptors is mainly restricted to tumor vessels. The causal involvement of this angiogenic factor in the progression of the disease has been successfully evaluated using monoclonal antibodies against vascular endothelial growth factor, dominant negative receptor mutants, and antisense oligonucleotides against the messenger RNA of vascular endothelial growth factor. Thus, the vascular endothelial growth factor-signaling system seems to be an appropriate target for inhibition of tumor angiogenesis and metastasis formation.
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PMID:Tumor angiogenesis: the pivotal role of vascular endothelial growth factor. 880 95

Continued tumor growth is dependent upon the growth of new blood vessels. This commentary reviews the mechanisms whereby tumors become vascularized and examines whether tumor angiogenesis is solely an example of a normal physiologic process or is part of the genetic program of the tumor. The likelihood that neovascularization of tumors combines both of these components, that is, utilizing tumor-specific elements as well as capacities common to all cells, is discussed.
Cancer Metastasis Rev 1996 Jun
PMID:Tumor angiogenesis: a physiological process or genetically determined? 884 92

Metastasis is the major cause of death in cancer patients. Our understanding of the molecular genetic and biologic events that contribute to tumor cell dissemination has increased considerably over the last decade. It is clear that close anatomic and temporal cooperation between cellular adhesion molecules, extracellular matrix-degrading proteases, and tumor vascularization is an essential component of the metastatic behavior of cancer cells. With this improved understanding have come novel antimetastatic therapies targeting distinct molecules and steps in the metastatic cascade. Here, we review the role of matrix-degrading enzymes, changes in cellular adhesive capacity, and tumor angiogenesis during cancer spread.
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PMID:Biology of tumor micrometastasis. 893 25

Clinical and experimental evidence suggests that spreading of malignant cells from a localized tumor (metastasis) is directly related to the number of microvessels in the primary tumor. This tumor angiogenesis is thought to be mediated by tumor-cell-derived growth factors. However, most tumor cells express a multitude of candidate angiogenesis factors and it is difficult to decipher which of these are rate-limiting factors in vivo. Herein we use ribozyme targeting of pleiotrophin (PTN) in metastatic human melanoma cells to assess the significance of this secreted growth factor for angiogenesis and metastasis. As a model we used human melanoma cells (1205LU) that express high levels of PTN and metastasize from subcutaneous tumors to the lungs of experimental animals. In these melanoma cells, we reduced PTN mRNA and growth factor activity by transfection with PTN-targeted ribozymes and generated cell lines expressing different levels of PTN. We found that the reduction of PTN does not affect growth of the melanoma cells in vitro. In nude mice, however, tumor growth and angiogenesis were decreased in parallel with the reduced PTN levels and apoptosis in the tumors was increased. Concomitantly, the metastatic spread of the tumors from the subcutaneous site to the lungs was prevented. These studies support a direct link between tumor angiogenesis and metastasis through a secreted growth factor and identify PTN as a candidate factor that may be rate-limiting for human melanoma metastasis.
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PMID:Melanoma angiogenesis and metastasis modulated by ribozyme targeting of the secreted growth factor pleiotrophin. 896 27

There is a worldwide increase in the incidence of melanoma. Without treatment, melanomas can progress to metastatic disease and result in death. It is now accepted that for a tumor to grow, non-tumorous host tissue must form blood vessels in and around the tumor. Tumor cells and blood vessels must form a highly regulated system whereby endothelial cells can be switched from a resting state to one of rapid growth. Tumor cells have been shown to produce diffusible angiogenic regulatory molecules. Nitric oxide [NO] and polyamines [PA] have been implicated in the angiogenic process. This paper hypothesizes that NO and PA regulate melanoma angiogenesis differently. During early stages of malignant melanoma an increase in PA synthesis is expected to promote endothelial cell proliferation and therefore angiogenesis. NO is expected to be maintained at low levels. During the vascular stage of malignant melanoma, NO synthesis is hypothesized to be elevated which will decrease endothelial cell proliferation and maintain a vasodilator tone in and around the tumor. PA concentrations are expected to be lower. A regulatory link between NO and PA may be involved in the maintenance of tumor homeostasis. The regulation of L-arginine metabolism in tumor angiogenesis requires investigation as it may lead to novel selective therapeutic interventions in cancer therapy.
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PMID:The importance of L-arginine metabolism in melanoma: an hypothesis for the role of nitric oxide and polyamines in tumor angiogenesis. 898 Oct 51

Physiologically, angiogenesis in adults is a controlled process which plays a role, for example, in wound healing. Pathological angiogenesis is observed in tumor formation and represents a multifactorial process, in which specific angiogenic factors, as well as growth factors, extracellular matrix proteins and cell adhesion molecules are involved. Tumor growth is characterized by an imbalance in favor of angiogenic over angiogenesis-inhibiting factors. Some of the most frequently examined angiogenic factors are vascular endothelial growth factor, acidic/basic fibroblast growth factors and the platelet-derived endothelial cell growth factor. The most important angiogenesis inhibitors are angiostatin and thrombospondin. To date, the clinical relevance of tumor angiogenesis has been shown for several human tumors. For most urological tumors, the grade of tumor vessel formation, measured as microvessel density, has been associated with metastases, tumor growth and clinical course. The prognostic value of this feature of malignant growth seems to be higher than that of most of the classical and newer prognostic factors. Systematic investigations of tumor angiogenesis are becoming increasingly relevant for diagnostic and therapeutic strategies and offer opportunities for the development of new specific therapeutic approaches in clinical oncology.
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PMID:[Angiogenesis--principles and significance in urologic tumors]. 899 26

Angiogenesis is a biologic process whereby endothelial cells divide and migrate to form new blood vessels. This process is required in physiological conditions, but is also a necessary requirement for solid tumors to grow and metastasize. Over the last several years, the growth factors that have both a positive and negative influence on tumor angiogenesis have been delineated. Interfering with tumor angiogenesis was considered a potential therapeutic strategy 25 years ago, but only recently have compounds with an ability to interfere with angiogenesis entered clinical trials. This review will discuss the first generation of angiogenesis inhibitors, their mechanism of action and data from clinical trials.
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PMID:An overview of clinical trials involving inhibitors of angiogenesis and their mechanism of action. 919 89

Binding of the serine protease urokinase (u-PA) to its receptor on tumor cell surfaces facilitates proteolysis and tumor invasion. We undertook this study to determine whether the role of u-PA in prostate cancer induced angiogenesis and secondary tumor growth by developing a homologous, immunocompetent in vivo model in which the tumors cells secrete an inhibitor of the murine u-PA receptor. A mutant recombinant murine u-PA that retains receptor binding but not proteolytic activity was made by PCR mutagenesis. Mutant u-PA and a reporter gene pRK luciferase were transfected and stably expressed in the highly metastatic rat Dunning MAT-LyLu prostate cancer cell line. Several clones expressing mutant u-PA and luciferase were identified by Western blotting, plasminogen zymography, and reverse transcription-PCR. One of these clones, 5C4, was injected s.c. into Copenhagen rats. Compared to animals injected with clones expressing pRK luciferase alone, tumors in animals injected with 5C4 cells were significantly smaller. Moreover, there were fewer lung micrometastases in the 5C4 animals. Primary tumor angiogenesis was measured by microvessel quantification of tissue stained with antibodies against von Willebrand factor. Mean microvessel density in 5C4 tumors was 4.3-fold lower than that in animals with tumors derived from the control tumor cell line (P < 0.0001). Significant inhibition of tumor growth was also observed for two additional MAT-LyLu cell lines expressing mutant u-PA. These findings suggest that cell surface u-PA contributes to prostate cancer growth by enhancing angiogenesis.
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PMID:Inhibition of prostate cancer neovascularization and growth by urokinase-plasminogen activator receptor blockade. 927 33

Angiogenesis, the formation of new capillaries from existing blood vessels, is necessary for embryonic growth and development. It is also seen later during the female cycle and wound healing, but is virtually absent otherwise in the healthy adult organism. Angiogenesis is again observed under pathological conditions, like for example in solid pediatric malignancies. Once grown to a diameter of several millimeters, the latter depend on angiogenesis in order to further grow and to metastasize. Recent experimental and clinical evidence suggests 1) that the extent of tumor angiogenesis could serve to predict clinical outcome and 2) that the inhibition of angiogenesis could be a means to improve the conventional therapy of solid pediatric malignancies.
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PMID:Clinical perspectives of tumor angiogenesis in pediatric oncology. 929 59


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