Katsuta Miwako, Miyashita Masao, Makino Hiroshi, Nomura Tsutomu, Shinji Seiichi, Yamashita Kiyohiko, Tajiri Takashi, Kudo Mitsuhiro, Ishiwata Toshiyuki, Naito Zenya
Surgery for Organ Function and Biological Regulation (Department of Surgery I), Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan.
Exp Mol Pathol. 2005 Apr;78(2):123-30. doi: 10.1016/j.yexmp.2004.11.002. Epub 2005 Jan 7.
Hypoxia inducible factor (HIF)-1alpha is a transcription factor that regulates the transcription of genes associated with cell proliferation and vascular development. In various cancer tissues, HIF-1alpha is associated with clinicopathological factors, such as the tumor size, histological grade, and lymph node status. Although HIF-1alpha plays a critical role in tumor growth by inducing vascular endothelial growth factor (VEGF), it is unclarified whether HIF-1alpha affects lymphatic metastasis. The purpose of this study is to clarify the correlation of HIF-1alpha protein expression with lymph node metastasis in esophageal squamous cell carcinoma (ESCC). The expressions of HIF-1alpha and VEGF-C, which is one of the main lymphangiogenic factors, were examined in five ESCC cell lines and 48 surgical specimens of ESCC. HIF-1alpha and VEGF-C mRNAs were expressed in all the five ESCC cell lines as determined by RT-PCR analysis. Immunohistochemically, 34 of the 48 patients (70.8%) were positive for HIF-1alpha and 29 patients (60.4%) were positive for VEGF-C. Clinicopathologically, HIF-1alpha expression correlated with lymphatic invasion and VEGF-C expression (P = 0.003 and P = 0.01, respectively). Furthermore, HIF-1alpha expression tended to correlate with lymph node metastasis (P = 0.09). These findings suggest that HIF-1alpha plays a role in lymphatic invasion and lymph node metastasis through the induction of VEGF-C in ESCC.
缺氧诱导因子（HIF）-1α是一种转录因子，可调节与细胞增殖和血管发育相关基因的转录。在各种癌症组织中，HIF-1α与临床病理因素相关，如肿瘤大小、组织学分级和淋巴结状态。尽管HIF-1α通过诱导血管内皮生长因子（VEGF）在肿瘤生长中起关键作用，但HIF-1α是否影响淋巴转移尚不清楚。本研究的目的是阐明食管鳞状细胞癌（ESCC）中HIF-1α蛋白表达与淋巴结转移的相关性。检测了5种ESCC细胞系和48例ESCC手术标本中HIF-1α和主要淋巴管生成因子之一VEGF-C的表达。通过RT-PCR分析确定，所有5种ESCC细胞系中均表达HIF-1α和VEGF-C mRNA。免疫组织化学检测显示，48例患者中有34例（70.8%）HIF-1α阳性，29例（60.4%）VEGF-C阳性。在临床病理方面，HIF-1α表达与淋巴管侵犯和VEGF-C表达相关（分别为P = 0.003和P = 0.01）。此外，HIF-1α表达倾向于与淋巴结转移相关（P = 0.09）。这些发现表明，HIF-1α在ESCC中通过诱导VEGF-C在淋巴管侵犯和淋巴结转移中发挥作用。
