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The microvesicle as a vehicle for EMMPRIN in tumor–stromal interactions

Oncogene volume 23, pages 956–963 (2004)Cite this article

Abstract

EMMPRIN is a transmembrane glycoprotein expressed at high levels by tumor cells. It has been identified as a tumor-derived factor that can stimulate matrix metalloproteinase expression in fibroblasts and hence facilitate tumor invasion and metastasis. Recent studies have shown that full-length EMMPRIN is released by tumor cells, but the mechanism of release remains unclear. Here, we show that EMMPRIN is released from the surface of NCI-H460 cells via microvesicle shedding. However, these vesicles are unstable and rapidly break down to release bioactive EMMPRIN. Although microvesicle shedding has been considered a constitutive process in tumor cells, our data show that it can be amplified upon cell exposure to PMA, elucidating at least one signalling cascade responsible for EMMPRIN release. This pathway is dependent on protein kinase C, calcium mobilization and mitogen-activated protein kinase kinase (MEK 1/2). Thus, the results outline a novel form of tumor–stromal interaction in which extracellular matrix degradation by fibroblasts is controlled through the microvesicular release of EMMPRIN from tumor cells.

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Acknowledgements

We thank Zena Werb, Ph.D. for helpful discussion and Marianne Gallup for expert assistance. The work was supported by NIH RO-1 HL 43762 (to CB) and PO-1 HL24136 (to CB) and a grant from the Tobacco-Related Diseases Research Program of the State of California (to CB).

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Authors and Affiliations

  1. Cardiovascular Research Institute and Department of Anatomy, Biomolecular Sciences Program, UCSF, San Francisco, 94143, CA, USA

    Sukhvinder S Sidhu, Aklilu T Mengistab & Carol Basbaum

  2. Cardiovascular Research Institute and Department of Anatomy, Biomedical Sciences and Neurosciences Programs, UCSF, San Francisco, 94143, CA, USA

    Andrew N Tauscher & Jennifer LaVail

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  1. Sukhvinder S Sidhu
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Correspondence to Carol Basbaum.

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Sidhu, S., Mengistab, A., Tauscher, A. et al. The microvesicle as a vehicle for EMMPRIN in tumor–stromal interactions. Oncogene 23, 956–963 (2004). https://doi.org/10.1038/sj.onc.1207070

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