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Signalling

Double trouble

Nature Reviews Cancer volume 13, pages 6–7 (2013)Cite this article

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Tumour growth was reduced only in Pld1−/− mice

To investigate non-cell-autonomous roles for PLD, the authors subcutaneously implanted syngeneic tumour cell lines (B16F10 melanoma cells and Lewis lung carcinoma cells) in Pld1- and Pld2-knockout mice, and found that tumour growth was reduced only in Pld1−/− mice. The tumours from Pld1−/− mice had a lower number of microvessels, suggesting a possible deficiency in angiogenesis. Indeed, vascularization was reduced in Matrigel plugs containing vascular endothelial growth factor (VEGF) that were implanted in Pld1−/− mice. Furthermore, endothelial cells from Pld1−/− aortic rings showed impaired migration, and primary Pld1−/− lung endothelial cells had a reduced ability to form tube-like structures in vitro. As these processes involve the regulation of endothelial cell adhesion to the extracellular matrix (ECM), the authors examined binding of Pld1−/− endothelial cells to various ECM proteins in vitro, and noted impaired binding to several integrin ligands. Integrins can be activated in response to VEGF receptor (VEGFR) signalling, and analysis of downstream pathways indicated that Pld1−/− endothelial cells had reduced VEGFR-dependent activation of p38 MAPK and AKT, which could explain the impaired integrin activation and adhesion in these cells, and therefore the reduced angiogenesis and primary tumour growth.

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ORIGINAL RESEARCH PAPER

  1. Chen, Q. et al. Key roles for the lipid signaling enzyme phospholipase D1 in the tumor microenvironment during tumor angiogenesis and metastasis. Sci. Signal. 5, ra79 (2012)

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  1. Sarah Seton-Rogers
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Seton-Rogers, S. Double trouble. Nat Rev Cancer 13, 6–7 (2013). https://doi.org/10.1038/nrc3421

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