Reduced expression of tissue factor pathway inhibitor-2 contributes to apoptosis and angiogenesis in cervical cancer

Abstract

BackgroundTissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix associated broad-spectrum Kunitz-type serine proteinase inhibitor. Recently, down regulation of TFPI-2 was suggested to be involved in tumor invasion and metastasis in some cancers.MethodsThis study involved 12 normal cervical squamous epithelia, 48 cervical intraepithelial neoplasia (CIN), and 68 cervical cancer. The expression of TFPI-2, Ki-67 and vascular endothelial growth factor (VEGF) were investigated by immunohistochemistry staining. The apoptolic index(AI) was determined with an in situ end-labeling assay(TUNEL). And the marker of CD34 staining was used as an indicator of microvessel density (MVD).ResultsTFPI-2 expression has a decreasing trend with the progression of cervical cancer and was significantly correlated with FIGO stage, lymph node metastasis and HPV infection. In addition, there were significant positive correlations between the grading of TFPI-2 expression and AI(P = 0.004). In contrast, the expression of TFPI-2 and VEGF or MVD was negatively correlated (both p < 0.001). However, we did not establish any significant correlation between Ki-67 and TFPI-2 expression in cervical cancer.ConclusionsThe results suggested that the expression of TFPI-2 had a decreasing trend with tumor progression of cervical cancer. There was a close association between the expression of TFPI-2 and tumor cell apoptosis and angiogenesis in patients with cervical cancer. TFPI-2 may play an inhibitive role during the development of cervical cancer.

Pregnancy complicated by obesity induces global transcript expression alterations in visceral and subcutaneous fat

“…TFPI-2 has also been associated with coagulation and fibrinolysis regulation (Zawadzki et al 2009). TFPI-2 interferes with the tissue factor (TF) pathway through inhibition of the TF-factor VIIa complex and reduced expression has been linked to many pathophysiological processes, including atherosclerosis and tumor growth (Zhang et al 2012),(Xiong et al 2010). Lower maternal plasma levels of TFPI-2 have been associated with preeclampsia (Matsuoka et al 1997; Hafner et al 2004).…”

Adipose tissue and adipocytes support tumorigenesis and metastasis

“…Poorly differentiated cancer cells are more autonomous and less dependent on the adipocyte microenvironment. Periprostatic and visceral adipose tissue has also been implicated in the support of prostate cancer cell growth and motility through the secretion of the MMP-9 [70]. Periprostatic adipose tissue was collected from patients undergoing prostatectomies and used to prepare conditioned-medium.…”

“…Cytokines secreted into the conditioned-medium were compared to corresponding patient serum. IL-6, a multifunctional cytokine involved in cell proliferation, angiogenesis and tumor progression, was excreted at high levels from adipose tissue and correlated with pathological grade of the tumor, compared to patient-matched serum [70;71]. Adipocytes may also provide lipid mediators to support prostate tumorigenesis, as evidenced by translocation of lipids from adipocytes to prostate cancer cells visualized by FTIR spectroscopy [72].…”

HIPK2-T566 autophosphorylation diversely contributes to UV- and doxorubicin-induced HIPK2 activation

“…HIPK2 dysregulation has been shown to contribute to proliferative diseases, such as cancer and tissue fibrosis [2, 26–28]. Based on our current knowledge, three possible mechanisms explaining the functional inactivation of HIPK2 have been proposed: the “localization model”, the “optimum model”, and the “PTM model” which foresee, respectively, tight regulations of HIPK2 subcellular localization, protein levels, and PTMs [18].…”