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M. Macfarlane

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    P1.01 - Poster Session 1 - Cancer Biology (ID 143)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.01-026 - Pro-tumorigenic alteration of signalling pathways in normal mesothelium: Contribution of non-mesothelial cells in malignant mesothelioma carcinogenesis (ID 1587)

      09:30 - 16:30  |  Author(s): M. Macfarlane

      • Abstract

      Malignant mesothelioma (MM) is an aggressive, fatal tumour of the pleura or peritoneum and strongly related to asbestos exposure. Malignant pleural mesothelioma (MPM) is the most common and occurs with a latency of up to 40 years. The mechanism of MM carcinogenesis is not well understood and the heterogeneity of the tumour is considered to be a major barrier to successful therapy. Several studies have identified changes in the expression and activities of defined cell signalling pathways in mesothelial and stromal cells, but the relationship between different cell types in the process of tumorigenesis has not been studied.

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

      Although the subcellular location of damage-associated molecular pattern (DAMP) protein HMGB1 remained nuclear in normal mesothelial cells co-cultured or treated with conditioned medium, the activation levels of growth modulating signalling pathways were altered in these cells. The proliferation and migration rates of normal mesothelial cells were also affected by paracrine signalling from activated fibroblasts and macrophages.

      Thus, non-mesothelial cells instigate alterations in cellular signalling in 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 mesothelioma carcinogenesis.