title: Elevated expression of thymosin β4, vascular endothelial growth factor (VEGF), and hypoxia inducible factor (HIF)-1α in early-stage cervical cancers.
abstract: Recent studies have shown that thymosin β4 (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-1α, 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-1α 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 -1α in cervical cancer metastasis. The expression levels of TB-4, VEGF, and HIF-1α 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-1α 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-1α 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-1α 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.
authors.affiliation: Department of Obstetrics and Gynecology, Kosin University College of Medicine, Busan, South Korea.
authors.forename: Nam Soo
authors.initials: NS
authors.lastname: Kim
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Kang
authors.forename: Jin-Ok
authors.initials: JO
authors.lastname: Jo
authors.forename: Heung Yeol
authors.initials: HY
authors.lastname: Kim
authors.forename: Young Rim
authors.initials: YR
authors.lastname: Oh
authors.forename: Young-Ok
authors.initials: YO
authors.lastname: Kim
authors.forename: Min Hyung
authors.initials: MH
authors.lastname: Jung
authors.forename: Mee Sun
authors.initials: MS
authors.lastname: Ock
authors.forename: Hee-Jae
authors.initials: HJ
authors.lastname: Cha
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D013947:Thymosin / Q000378:metabolism*; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D000099201:Thymosin beta(4)
chemical_list: D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D013947:Thymosin; D042461:Vascular Endothelial Growth Factor A; D000099201:Thymosin beta(4); C497442:HIF1A protein, human; C467484:VEGFA protein, human