Osteopontin Isoforms as Diagnostic Markers for Mesothelioma

Prior research has identified osteopontin (SPP1) as a potential tumor marker for malignant mesothelioma, as well as for other cancers, but little is understood about the biological activity responsible for this function. Molecular analysis of osteopontin has identified three specific isoforms of the protein, which are known as SPP1-A, SPP1-B and SPP1-C, but the relationship between these isoforms and carcinogenesis is also poorly understood. To learn more about these relationships, researchers from New York University’s School of Medicine conducted a study on tissue samples extracted from the resected tissue of patients with malignant mesothelioma and then compared their findings to a control group of healthy tissue. The researchers found that all of the isoforms of SPP1 were present in normal tissues, but that SPP1-A and SPP1-B were significantly up-regulated in the mesothelioma tissue, but SPP1-C was not. This was also the case when the researchers compared cases of primary mesothelioma to cases of recurrent mesothelioma, which led the researchers to conclude that SPP1-A and SPP1-B may be useful serum markers for mesothelioma diagnosis.
The researchers also looked at the tumorigenic activity of osteopontin and found that both SPP1-A and SPP1-B were associated with pro-tumorigenic activity, while SPP1-C was not. The researchers hypothesize that because the only structural difference between SPP1-A and SPP1-C is an exon that encodes an oligopeptide, future research may be able to develop a specific inhibitor to SPP1-A’s pro-tumorigenic activity. Such a development could be very beneficial to improving the efficacy of mesothelioma treatments.

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About Mesothelioma

Mesothelioma is an asbestos-caused cancer of the membranes that surround many of the body’s vital organs. This membrane, known as mesothelium, secretes a lubricating fluid that provides easy movement of the organs within the body. When the mesothelium becomes cancerous, it is called mesothelioma. Surrounding the lung, the mesothelium is called the pleura and the form of mesothelioma is called pleural mesothelioma; in the abdomen, it is the peritoneum and the cancer is called peritoneal mesothelioma; the lining around the heart is the pericardium and there mesothelioma is identified as pericardial mesothelioma. There is also mesothelial tissue in the reproductive organs: in males, this tissue is called the tunica vaginalis testis and in women the tunica serosa uteri. Mesothelioma of the reproductive tissues has only presented in men, so it is known as mesothelioma of the tunica vaginalis. 
Mesothelioma is a diffuse malignancy and spreads itself throughout a tissue area. Some forms of cancer are characterized by a single, solid tumor mass, whereas malignant mesothelioma presents as an invasion of a large number of smaller masses throughout an entire area. The diffuse nature of mesothelioma has important implications for how mesothelioma is treated, as complete surgical extraction of the cancerous tissue is difficult.

Types of Mesothelioma

There are multiple forms of mesothelioma. The differences involve the location in which the tumor begins, known as its origin site, and the type of cells that the tumor invades, known as its histological subtype.

Location of Disease

The most common form of mesothelioma is pleural mesothelioma, where the cancer attacks the pleural tissue surrounding the lung. As many as eighty percent of all mesothelioma diagnoses are for pleural mesothelioma. The pleura’s proximity to the lung is the reason many people mistakenly think of mesothelioma as lung cancer, which it is not. Pleural mesothelioma can spread (“metastasize”) to the lung, but the origin site is the actual pleural tissue surrounding the lung—not the lung itself. There are many differences between mesothelioma and lung caner.
After pleural mesothelioma, the next most common type is peritoneal mesothelioma, which develops in the majority of other cases. There is some evidence to suggest that diagnoses of mesothelioma are on the rise. While pericardial mesothelioma and mesotheliomas of the tunica vaginalis are also possible forms of the disease, they are very rare tumors and occur less often.

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