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IStat1 negatively regulates angiogenesis, tumorigenicity and metastasis of tumor cells. Between 1970 and 1994, cancer claimed the lives of about 0.5 million Americans every year. According to the most recent statistics, it is estimated that approximately 1.3 million new cases of cancer will be diagnosed and 555,500 people will die from cancer in the United States in the year 2002. As a result considerable effort is being expended to speed the development of effective cancer therapies. Stimulators of apoptosis and inhibitors of angiogenesis represent two of the fastest growing areas of oncology. The "Signal Transducers and Activators of Transcription" (STAT) pathway has recently emerged as a target for molecules designed to block angiogenesis. Since their discovery as key mediators of cytokine signaling, considerable progress has been made in defining this pathway. In addition to its central role in normal cell signaling, STAT1 has been shown to mediate growth inhibitory signals. Now field leaders from The University of Texas MD Anderson Cancer Center have provided direct evidence linking STAT1 with tumor progression. This group developed a highly tumorigenic and metastatic RAD-105 tumor cell line from a fibrosarcoma of a Stat1 knockout mouse. Reconstitution of Stat1 suppressed the tumorigenicity and metastasis of RAD-105 cells in nude mice which correlated with a decreased microvessel density and decreased expression of proangiogenic molecules ßFGF, MMP-2, and MMP-9 in vivo. Moreover, non-cytotoxic concentrations of IFN-ß significantly inhibited the in vitro expression of ßFGF in the Stat1-reconstituted cells but not in the Stat1-deficient cells. Therefore, STAT1 is an important mediator for antiangiogenic signals, such as IFN. Collectively, these data demonstrate that Stat1 expressed by tumor cells is a negative regulator of tumor angiogenesis and, hence, tumor growth and metastasis. Strategies designed to further activate STAT1 are likely to reduce angiogenesis in their own right and also to enhance the therapeutic activity of IFN-related molecules, and therefore deserve the attention of the pharmaceutical industry Link to journal abstract:
Adapted from Huang et al, Oncogene 2002 Apr 11;21(16):2504-12 Interested in collaborating with this group? Contact leaddiscovery@bioportfolio.co.uk LeadDiscovery and BioPortfolio aims to provide reliable, insightful analysis on the biotechnology industry. However, this information is provided "as is" and no representations or warranties either express or implied of completeness, accuracy, or of any other nature are made with respect to this information. This information is neither an offer to sell nor a solicitation to buy the securities of any company. This information contains forward-looking statements, which involve risks and uncertainties which may not be listed. The biotechnology industry is an emerging industry and the securities of the companies mentioned in this report have a very high degree of risk and volatility. For this reason, this information is supplied on the condition that the reader will make his or her own determination as to its suitability for any purpose prior to any use of this information. The employees and officers of LeadDiscovery and BioPortfolio may hold positions in some or all of the stocks discussed in this report. This abstract has been produced by LeadDiscovery Ltd. Founded by life scientists for life scientists we aim to help industry identify cutting edge drug discovery options and academic/biotech institutions maximize the potential of their research. Abstracts strictly reflect the opinion of LeadDiscovery's editorial panel. While all reasonable efforts are made to ensure the accuracy of information provided LeadDiscovery and the publisher BioPortfolio, takes no responsibility for incorrect or misleading information. LeadDiscovery is designed for educational and drug development purposes only and is not intended or designed to offer medical advice or advice of any sort, and must not be used for such purpose. The information provided through LeadDiscovery and BioPortfolio should not be used for diagnosing or treating a health problem or a disease and no reliance should be placed on any information contained in this abstract or elsewhere on LeadDiscovery's and BioPortfolio's website. It is not intended to be a substitute for professional care. If you have or suspect you may have a health problem, you should consult your physician or other health care provider. |
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