BACKGROUND AND AIMS: The administration of endostatin, a potent anti-angiogenic agent, will be required for extended periods of time as a cancer treatment. The aim of the present study was to induce endogenous endostatin secretion in a continuous fashion, based on retroviral gene transfer. The tumor response was evaluated in an orthotopic murine tumor model of human lung cancer. MATERIALS AND METHODS: Human non-small-cell lung cancer cells (KNS 62) were retrovirally transduced with the human endostatin gene. An orthotopic murine xenotransplant model was used to investigate tumor growth, metastases and survival. After 4 weeks of subcutaneous growth, endostatin expression was measured by immunoblot analysis in tumor lysates. RESULTS: The growth of the subcutaneous tumors was significantly delayed, and orthotopic tumor growth and pleural metastases were significantly reduced in endostatin-transduced KNS 62 tumors. Prolongation of survival subsequent to orthotopic tumor induction was demonstrated. Strong endostatin expression was found in subcutaneous tumors after 4 weeks. CONCLUSION: Retroviral transduction of the human endostatin gene is capable of achieving long-term endostatin expression. Endostatin transduction provides significant anti-tumor effects with regard to local tumor growth, metastases and survival.
BACKGROUND AND AIMS: The administration of endostatin, a potent anti-angiogenic agent, will be required for extended periods of time as a cancer treatment. The aim of the present study was to induce endogenous endostatin secretion in a continuous fashion, based on retroviral gene transfer. The tumor response was evaluated in an orthotopic murinetumor model of humanlung cancer. MATERIALS AND METHODS:Human non-small-cell lung cancer cells (KNS 62) were retrovirally transduced with the humanendostatin gene. An orthotopic murine xenotransplant model was used to investigate tumor growth, metastases and survival. After 4 weeks of subcutaneous growth, endostatin expression was measured by immunoblot analysis in tumor lysates. RESULTS: The growth of the subcutaneous tumors was significantly delayed, and orthotopic tumor growth and pleural metastases were significantly reduced in endostatin-transduced KNS 62 tumors. Prolongation of survival subsequent to orthotopic tumor induction was demonstrated. Strong endostatin expression was found in subcutaneous tumors after 4 weeks. CONCLUSION: Retroviral transduction of the humanendostatin gene is capable of achieving long-term endostatin expression. Endostatin transduction provides significant anti-tumor effects with regard to local tumor growth, metastases and survival.
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