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Intermittent hypoxia induces tumoral angiogenesis in mouse melanoma metastasis model.
Department of Pharmacology, Seoul National University College of Medicine©ö, Department of Otorhinolaryngology Head and Neck Surgery, Seoul National University Hospital©÷, Department of Biological Science, Korea Advanced Institute of Science and Technology©ø
Daeho So©ö, Jiyoung Kim©ö, Eunji Kong©ø, Mingyu Lee©ö, Dae-Wui Yoon©ö, Chung-Hyun Cho©ö, Jong-Wan Park©ö, Hyun-Woo Shin©ö,©÷
¸ñÀû: Obstructive Sleep Apnea (OSA) is characterized by repetitive occlusions of the upper airway that lead to chronic intermittent hypoxia (CIH), thus showing as recurrent blood oxygen desaturations. Recent human studies reported that the cancer incidence and mortality of OSA patients are higher than normal controls. So, the aim of this study was to evaluate the effect of the intermittent hypoxia on cancer metastasis in mice. ¹æ¹ý:C57BL/6 mouse were placed in the OxyCycler chambers (Biospherix, Inc) on normoxic or intermittent hypoxic condition in 8 hrs of alternating cycles with 21% and 12% of oxygen for 120 seconds on each oxygen concentration for 7 days. Then B16F10 melanoma cells were injected into the tail vein of C57BL/6 mouse and bred in normoxic or intermittent hypoxic condition as above. After 24 days, the mice were sacrificed, and lung metastasis was investigated by histological examination. PCNA, HIF-1a, CD31 expressions were measured with immunohistochemistry. °á°ú:Compared with normoxia, CIH has no pronounced effect on melanoma metastasis in terms of metastatic lung nodules and histological lung section. However, PCNA, which was important marker for cell proliferation and division, and HIF-1¥á, transcription factors that respond to changes in oxygen concentration, protein expressions were slightly increased. The noticeable thing is that CD31, which was a marker of the endothelial cells in blood vessels, protein expression was increased about two-fold in lung. °á·Ð:This study shows that CIH might not promote B16F10 melanoma metastasis to lung. However, considering the higher expression of CD31 in metastatic nodules in CIH, it could be thought that CIH affects tumoral angiogenesis in metastatic nodules, possibly leading to the cancer progression and poor survival.


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