Functional expression of TWEAK and the receptor Fn14 in human malignant ovarian tumors: possible implication for

Liying Gu1, Lan Dai, Cong Cao

  • 1Department of Gynecology and Obstetrics, Renji Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, PR China.

Plos One
|March 8, 2013
PubMed

Insights

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are expressed in malignant ovarian tumors, suggesting a potential tumor suppressor role by activating macrophages and serving as a diagnostic marker.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The expression and role of TWEAK/Fn14 in ovarian cancer are not fully understood.
  • Ovarian cancer remains a significant health challenge with a need for novel diagnostic markers and therapeutic targets.

Purpose of the Study:

  • To investigate the expression of TWEAK and Fn14 in human ovarian tumors.
  • To elucidate the role of TWEAK in ovarian cancer progression in vitro.
  • To explore the potential of TWEAK/Fn14 as a diagnostic marker for malignant ovarian tumors.

Main Methods:

  • Immunohistochemistry (IHC) was used to detect TWEAK and Fn14 expression in human ovarian tumor tissues.
  • In vitro cell culture models (HO-8910PM cells and THP-1 macrophages) were employed to study TWEAK's effects on proliferation, invasion, and cytokine production.
  • Conditioned media from activated macrophages were used to assess their impact on ovarian cancer cells.

Main Results:

  • TWEAK and Fn14 were significantly expressed in malignant ovarian tumors but absent in normal or benign tissues.
  • TWEAK alone or TNF-α alone did not inhibit HO-8910PM cell proliferation; combined TWEAK and TNF-α showed an inhibitory effect.
  • TWEAK activated macrophages to produce TNF-α and MCP-1, and conditioned media from these activated macrophages inhibited ovarian cancer cell proliferation and invasion.

Conclusions:

  • TWEAK/Fn14 signaling, through macrophage activation, may act as an ovarian tumor suppressor mechanism.
  • The specific expression of TWEAK/Fn14 in malignant ovarian tumors suggests its potential utility as a diagnostic biomarker.

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
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...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...