Pathogenesis of Mesothelioma

There are three types of mesothelioma: epithelial (or tubulopapillary); mesenchymal (or fibrosarcomatous) and mixed (or biphasic), where the patient is diagnosed with both the epithelial and mesenchymal forms of the disease. The inhaling of asbestos particles or dust is almost universally the primary cause of mesothelioma.

Asbestos fibers, once inhaled into the lungs, can do damage in several different ways. The fibers can irritate the pleura, or the lining of the lungs and over time can penetrate it. Once the fibers penetrate into the lungs, they can produce scarring (or plaques) or begin a process that results in malignant mesothelioma.

Asbestos fibers can also penetrate DNA chromosomes and become entangled with them. The fibers are also capable of severing the DNA spindle; both can cause abnormalities than can develop into cancerous activity. This normally happens when the fibers eliminate tumor suppressors that limit the spread of cancerous cells. Asbestos fibers are also capable of aiding the entry of foreign DNA into target cells. This can lead to mutations and oncongenesis, or the altering of normal cells into cancerous ones.

The fibers can also sever or pierce the mitotic spindle of cells and disrupts normal mitosis, or cell division. This can result in aneuploidy, or an unusual number of chromosomes, which can lead to an increased risk of cancer. It can also cause other kinds of chromosome damage.

Cytogenetic analysis of malignant mesothelioma shows that the cancerous cells frequently suffer from severe damage caused by asbestos fibers. These include having abnormal karyotypes, or chromosome makeups. They also tend to have undergone extensive aneuploidy and structural rearrangement. Mesothelioma cells exhibit much faster and less regulated growth than healthy cells and are capable of stimulating themselves internally, without introducing growth factors from the outside.

Mesothelioma tumors require the constant formation of blood vessels to continue to grow and are capable of producing elements that can lead to the existence of the vascular endothelial growth factor in more severe cases. Malignant mesothelioma cells are also capable of creating collagen, or the primary protein in making tissue, making the cancer more painful for the sufferer. The tumors also cause inflammation, due to both the malignant process and the strains of asbestos themselves.

Healthy cells can be killed by the activation of their "death receptors." Malignant mesothelioma cells have higher levels of the molecule and doctors have connected higher numbers of healthy cell deaths with the presence of malignant mesothelioma. Much research in the area now focuses on the mechanisms of mesothelial cell transformation, and on development of methods to kill the tumor cells.

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