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    P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
    • Presentations: 1
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      P3.08-016 - Role of Pro-Inflammatory Cells in Development of Mesothelioma (ID 445)

      09:30 - 09:30  |  Author(s): F. Murphy

      • Abstract
      • Slides

      Background:
      Malignant mesothelioma is an aggressive tumour of the pleura or peritoneum and strongly related to asbestos exposure. Malignant pleural mesothelioma is the most common and occurs with a latency of up to 40 years. Long pathogenic fibres fail to clear through the lymph system and are retained in the pleura of the exposed individuals. During the long latency period, mesothelial cells remain exposed to paracrine signalling from inflammatory cells recruited to the fibre-retaining areas. However, the mechanism of malignant transformation is not well understood. Several studies have identified changes in defined signalling pathways in mesothelial and stromal cells, but the relationship between different cell types has not been explored.

      Methods:
      To examine the pro-oncogenic role(s) of different cell populations, the effect of primary fibroblasts from human mesotheliomas and fibre-activated macrophages on cellular signalling in normal untransformed mesothelial cells was monitored using imaging and immunoblotting techniques.

      Results:
      Paracrine signalling from activated fibroblasts or macrophages increased the levels of proliferation and motility in normal mesothelial cell cultures. Activation of pro-oncogenic signalling was demonstrated in the cultures subjected to ‘cross-talk’ with pro-inflammatory cells, including ‘horizontal transfer’ from activated fibroblasts. Normal mesothelial cells, co-cultured or treated with conditioned media from fibre-activated macrophages, also displayed signs of epithelial-to-mesenchymal transition. The levels of growth modulators and survival rates were also altered in these cells.

      Conclusion:
      Thus, non-mesothelial cells instigate pro-oncogenic alterations in cellular signalling in target mesothelial cells. Further integral examination of the aberrant signalling pathways, especially at early stages of neoplasia, will provide new insights into the mechanisms underlying malignant transformation of the mesothelium.

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