Tumor necrosis factor

Definition

Tumor necrosis factor is a protein produced by several of the body's cell types, such as white blood cells, red blood cells, and other cells that line the blood vessels. It promotes the destruction of some types of cancer cells.

Description

In the 1970s, researchers took sarcoma cells in culture and exposed them to a protein produced by white blood cells. The protein caused necrosis (death) of the sarcoma cells but had little effect on normal cells in the culture. Hence, the protein was called "tumor necrosis factor" (TNF).

TNF is a type of cytokine released by white blood cells. Cytokines are a group of molecules that are released by many different cells to communicate with other cells and regulate the duration of an immune response . There are many different kinds of cytokines, each with a different effect on specific target cells. Once a cell releases the cytokines, they bind to corresponding receptors located on target cells, thus causing a change to take place within the target cell. Tumor necrosis factor is released by special white blood cells called macrophages. Although researchers are still investigating the exact mechanism by which TNF kills cancer cells, it is clear that TNF binds to receptors located on the surface of cancer cells, causing a change and then death of the cell. This was found to be true in animal models. As a result, researchers thought TNF might enhance the reaction of the human immune system to cancer cells.

In the mid-1980s, TNF became available in recombinant form and was analyzed in clinical human trials. At that time, researchers discovered that TNF administered systemically was toxic to humans' normal tissues at the maximum doses required to kill all of the cancer cells, thus limiting its usefulness. At maximum doses required to kill cancer cells, patients experienced fever , loss of appetite (anorexia ), and cachexia (severe weight loss , malnutrition, and wasting away of the body).

However, TNF can be effectively combined with other systemic chemotherapeutic drugs such as doxorubicin and etoposide . TNF in conjunction with the above drugs enhances DNA breakage in tumor cells, contributing to their death. In addition to administering TNF systemically, TNF (with or without other chemotherapeutic drugs) can be forced through the blood at the capillary beds at or near the site of the tumor. The regional perfusion of TNF allows larger dosages to be administered only in the area requiring the treatment. Therefore, less normal and healthy tissue is disrupted before reaching the maximum tolerable limits. Research performed in 1998 (by Lejeune, et al.) found regional perfusion to be especially successful in the case of melanomametastasis , resulting in complete remission of 70% to 80% of patients.

Although TNF is valuable in killing cells in melanoma and sarcoma tumors, it can promote growth of other kinds of cancers. Therefore, the action of TNF is continually under research with the hope of increasing its effectiveness on killing cancer cells, while decreasing the toxic side effects on healthy tissue.

Sally C. McFarlane-Parrott

KEY TERMS

Cachexia

—A side effect of cancer therapy characterized by weight loss due to lack of appetite and wasting away due to malnutrition.

Cytokines

—Molecules released by cells to regulate the length and intensity of an immune response and to mediate intercellular communication.

Macrophage

—A type of white blood cell that produces antibodies and molecules for cell-to-cell immune responses.

Regional perfusion

—Forcing a liquid through the blood at the capillary beds at or near a specific site.

tumour necrosis factor (TNF) Either of two proteins that act as cytokines, eliciting numerous responses in virtually all types of cells by activating cellular signalling pathways and promoting the expression of genes. They are involved in many aspects of the body's immune defences, notably in their ability to destroy tumour cells; they also assist in the killing of virally infected cells by natural killer cells. TNF-α is a glycoprotein produced chiefly by monocytes and macrophages, whereas TNF-β is produced by T cells. Both bind to the same sets of cell-surface receptors.

tumour necrosis factor (TNF) either of two proteins, TNF-α (produced mainly by monocytes and macrophages) or TNF-β (produced by lymphoid cells), that act as mediators for immune responses. Among their many actions is destruction of tumour cells.