The role of TNF-α in chordoma progression and inflammatory pathways

Sukru Gulluoglu1,2, Emre Can Tuysuz1,2, Mesut Sahin3

  • 1Department of Medical Genetics, Yeditepe University Medical School, Koftuncu Sok. Acıbadem Mah. Istek Vakfi Kat: 3 34718 No: 57/1 Kadikoy, 34755, Istanbul, Turkey.

Abstract

Insights

Tumor necrosis factor-alpha (TNF-α) promotes chordoma progression by increasing cell migration, invasion, and chemo-resistance. Elevated TNF-α correlates with poor prognosis and tumor-promoting inflammation in chordoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Chordomas are aggressive primary bone tumors known for therapy resistance and high recurrence rates.
  • These tumors can cause significant local destruction, posing a therapeutic challenge.

Purpose of the Study:

  • To investigate the impact of tumor necrosis factor-alpha (TNF-α) on chordoma progression.
  • To evaluate the relationship between TNF-α and clinical outcomes in chordoma patients.

Main Methods:

  • Chordoma cells were treated with TNF-α, and effects on chemo-resistance, epithelial to mesenchymal transition (EMT), migration, and stem cell properties were assessed.
  • Gene expression (qRT-PCR, microarray) and functional assays were employed.
  • Correlation between TNF-α expression and patient clinicopathological features was analyzed.

Main Results:

  • TNF-α enhanced chordoma cell migration, invasion, and chemo-resistance, alongside increased EMT marker expression and NF-κB activation.
  • Enhanced tumor sphere and soft agar colony formation, indicative of stem-like properties, were observed.
  • High TNF-α and TNFR1 expression correlated with tumor volume, poor survival, and elevated LIF, PD-L1, and Ki67 levels.

Conclusions:

  • TNF-α may act as a prognostic biomarker for chordoma progression.
  • Tumor-promoting inflammation, mediated by factors like TNF-α, appears crucial in chordoma advancement.

Related Concept Videos

Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
7.0K
C4 Pathway and CAM01:27

C4 Pathway and CAM

Most plants use the C3 pathway for carbon fixation. However, some plants, such as sugar cane, corn, and cacti that grow in hot conditions, use alternative pathways to fix carbon and conserve energy loss due to photorespiration. Photorespiration is the process that occurs when the oxygen concentration is high. Under such conditions, the rubisco enzyme in the Calvin cycle binds O2 instead of CO2, which halts photosynthesis and consumes energy.
C4 Pathway
The C4 pathway is used by plants such as...
48.9K
Inflammatory Response01:28

Inflammatory Response

An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
16.1K
Inflammatory Response II: Inflammatory Exudate and Tissue Repair01:24

Inflammatory Response II: Inflammatory Exudate and Tissue Repair

The immune system's inflammatory response destroys the invading pathogen, permitting the tissue to heal. The changes during the cellular and vascular stages allow exudate formation at the site of inflammation. The inflammatory exudate released from the wound has high protein content and a specific gravity above 1.020.
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the...
7.5K
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...
7.3K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
519