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Y.Y. Cheng



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    P2.14 - Poster Session 2 - Mesothelioma (ID 196)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Mesothelioma
    • Presentations: 1
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      P2.14-008 - Effect of Aquaporin 1 Modulation in Malignant Pleural Mesothelioma: Inhibition of Cell Proliferation and Colony Formation in vitro and Tumour Growth in vivo using a Heterotopic Mouse Model (ID 2615)

      09:30 - 09:30  |  Author(s): Y.Y. Cheng

      • Abstract

      Background
      Aquaporin 1 (AQP1) has been shown to be an independent prognostic marker for survival in malignant pleural mesothelioma (MPM). AQP1 is a trans-membrane protein normally expressed in mesothelial cells and is part of a family of proteins involved in fluid homeostasis, cell proliferation and motility. AQPs have been implicated in various aspects of tumour development. The aim of the current study was to determine the functional role of AQP1 in MPM, using in vitro and in vivo models.

      Methods
      Primary MPM cells obtained from patient’s pleural effusions and the MPM cell line NCI-H226 were subjected to a specific pharmacological AQP1 blocker and AQP1 siRNA knockdown and examined for proliferation and colony formation using MTS and anchorage independent assays. Levels of AQP1 expression were determined by immunohistochemistry and RT-PCR. The influence of AQP1 on tumour growth in vivo was studied using a heterotopic mouse model. Briefly, 5 x 10[6] NCI-H226 cells were injected subcutaneously in the hind flank of BALB/C nude mice and allowed to grow to 100 mm[3] before daily intra-tumour injections of AQP1 blocker. Tumour size was measured daily.

      Results
      AQP1 expression correlates with cell proliferation in primary MPM cells (R[2] = 0.69). Blockade of AQP1 with pharmacological blocker or siRNA knockdown in MPM cells was shown to significantly decrease cell proliferation, both in NCI-H226 (p < 0.05) and primary MPM cells expressing AQP1 (p < 0.05). Primary MPM, where more than 20% of tumour cells expressed AQP1, showed greater reduction in proliferation compared to cells having AQP1 expression <20%. Application of AQP1 blocker decreased both the number and size of colonies formed after NCI-226 cells were subjected to anchorage independent growth (p < 0.05). In a pilot study using the heterotopic mouse model the size of tumours was decreased after 5 days using 20 μM of AQP1 blocker compared to an untreated control (n=6 for each group).

      Conclusion
      Results indicate that AQP1 plays a functional role in MPM. Modulation of AQP1 decreases cell proliferation and colony formation as well as the growth of MPM tumours in a heterotopic mouse model. Larger scale animal studies are required to further understand the role of AQP1 in MPM and the potential clinical implications of an AQP1 blocker in the treatment of MPM