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

Qiao Zhang1, Yao Zhang, Shi Z Wang

  • 1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.

Abstract

Insights

Tissue factor pathway inhibitor-2 (TFPI-2) expression decreases with cervical cancer progression. Lower TFPI-2 levels correlate with increased tumor cell apoptosis and angiogenesis, suggesting an inhibitory role in cervical cancer development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor associated with the extracellular matrix.
  • Downregulation of TFPI-2 has been implicated in tumor invasion and metastasis in various cancers.

Purpose of the Study:

  • To investigate the expression of TFPI-2 in normal cervical squamous epithelia, cervical intraepithelial neoplasia (CIN), and cervical cancer.
  • To determine the correlation between TFPI-2 expression and clinicopathological features, including tumor stage, lymph node metastasis, HPV infection, apoptosis, and angiogenesis.

Main Methods:

  • Immunohistochemistry was used to assess the expression of TFPI-2, Ki-67, and vascular endothelial growth factor (VEGF).
  • Apoptotic index (AI) was determined using an in situ end-labeling assay (TUNEL).
  • Microvessel density (MVD) was evaluated using CD34 staining.

Main Results:

  • TFPI-2 expression showed a decreasing trend with cervical cancer progression and was significantly correlated with FIGO stage, lymph node metastasis, and HPV infection.
  • TFPI-2 expression positively correlated with AI (P=0.004) and negatively correlated with VEGF and MVD (p < 0.001).
  • No significant correlation was found between Ki-67 and TFPI-2 expression in cervical cancer.

Conclusions:

  • TFPI-2 expression decreases as cervical cancer progresses.
  • TFPI-2 expression is closely associated with tumor cell apoptosis and angiogenesis in cervical cancer.
  • TFPI-2 may exert an inhibitory effect on the development of cervical cancer.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.