Pleural Mesothelioma and Its Possible Link to Inflammatory Macrophage MIF Continues to Baffle

Pleural Mesothelioma and Its Possible Link to Inflammatory Macrophage MIF Continues to Baffle

The inflammatory macrophage migration inhibitory factor (MIF) might affect the development of malignant pleural mesothelioma. A study into the factor’s effect on cells derived from different mesothelioma cell types and stages, however, showed a rather confusing picture, signaling the need for further studies on the inflammatory mediator in living models.

The study, Role of MIF/CD74 signaling pathway in the development of pleural mesothelioma, was published in the journal Oncotarget.

Cancer research, investigating other types of cancer, has reported that MIF might be involved in the multiplication process of cancer cells, and scientists have observed a link between MIF levels and cancer prognosis. The factor is produced by cells associated with tumors, such as macrophages and fibroblasts.

The research team from University Hospitals and University of Geneva, Switzerland, investigated the role of MIF and its receptor, called CD74, in six different lines of cultured cells derived from mesothelioma patients, as well as in one cell line derived from non-cancerous human mesothelium. The six mesothelioma cell lines were originally derived from different subtypes of cells.

Researchers noted that all the cells derived from cancers had high numbers of the MIF receptor CD74, but secreted lower levels of the factor itself, compared to cells from normal mesothelium. This suggested that mesothelioma cells are more sensitive to MIF than normal cells. In cells with higher levels of both MIF and its receptor, the research team noted higher multiplication rates, and the cells seemed to be protected from cell death. When the team blocked both MIF and its receptor the situation was reversed, with cells multiplying less, and dying more.

But when researchers injected mice with cells from two of the cell lines expressing high levels of CD74, and two with low levels of the receptor, they noted that higher levels of CD74 were linked to a lower cell potential to grow tumors.

These extensive differences are likely explained by the environment in which the tumor cells find themselves. Cells in culture are surrounded by a standardized environment in the form of growth medium, while cells in the body are exposed to an array of signals both from neighboring cell types and factors present in the blood.

Previous experiments by the group showed that in human mesothelioma tissue, not exposed to culture conditions, low CD74 levels were associated with low patient survival rates, a situation resembling the mice experiments. It is, therefore, crucial to continue to study the role of MIF and its receptor in animal models of the disease.

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