Elevated Expression of Thymosin β4, Vascular Endothelial Growth Factor (VEGF), and Hypoxia Inducible Factor (HIF)-1α in Early-Stage Cervical Cancers

Recent studies have shown that thymosin beta 4 (TB-4) is highly related with tumor metastasis and angiogenesis. In addition, TB-4 induced the expression of VEGF in melanoma cells. We investigated the expression patterns of TB-4 and related angiogenic proteins, VEGF, and HIF-1 alpha, at various stages of cervical cancers and also identified the expression pattern of these proteins in metastatic cervical cancers. Expression patterns of TB-4, VEGF, and HIF-1 alpha were studied with tissue microarray containing 42 samples of cervical cancers. In addition, 15 cervical cancers and metastatic tumors in lymph nodes from patients who have metastatic tumors were also analyzed to confirm the role of TB-4, VEGF, and HIF -1 alpha in cervical cancer metastasis. The expression levels of TB-4, VEGF, and HIF-1 alpha were very weak at early cancer stages (stages 0 to 1A) but significantly increased at stage 1B. The numbers of blood vessels in tumors were also increased at stage 1B. The expression patterns of TB-4, VEGF, and HIF-1 alpha were compared in tumors without lymph node metastasis, primary tumors with lymph node metastasis, and metastatic tumors in lymph nodes. The expression levels of TB-4, VEGF, and HIF-1 alpha in primary tumors with lymph node metastasis and their metastatic tumors in lymph node were less than in tumors without lymph node metastasis. These data suggest that TB-4, VEGF, and HIF-1 alpha triggered angiogensis and tumor invasiveness to surrounding tissues at early stage of cervical carcinoma but have a negative or no effect on the metastatic potential.