Cyclin D1 governs adhesion and motility of macrophages

Peter Neumeister, Fiona J. Pixley, Ying Xiong, Huafeng Xie, Kongming Wu, Anthony Ashton, Michael Cammer, Amanda Chan, Marc Symons, E. Richard Stanley, Richard G. Pestell

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that phosphorylates and inactivates the retinoblastoma protein, thereby promoting cell-cycle progression. Cyclin D1 is overexpressed in hematopoetic and epithelial malignancies correlating with poor prognosis and metastasis in several cancer types. Because tumor-associated macrophages have been shown to enhance malignant progression and metastasis, and cyclin D1-deficient mice are resistant to oncogene-induced malignancies, we investigated the function of cyclin D1-/- bone marrow-derived macrophages. Cyclin D1 deficiency increased focal complex formation at the site of substratum contact, and enhanced macrophage adhesion, yielding a flattened, circular morphology with reduced membrane ruffles. Migration in response to wounding, cytokinemediated chemotaxis, and transendothelial cell migration of cyclin D1-/- bone marrowderived macrophages were all substantially reduced. Thus, apart from proliferative and possible motility defects in the tumor cells themselves, the reduced motility and invasiveness of cyclin D1-/- tumor-associated macrophages may contribute to the tumor resistance of these mice.

Original languageEnglish (US)
Pages (from-to)2005-2015
Number of pages11
JournalMolecular biology of the cell
Volume14
Issue number5
DOIs
StatePublished - May 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Neumeister, P., Pixley, F. J., Xiong, Y., Xie, H., Wu, K., Ashton, A., Cammer, M., Chan, A., Symons, M., Stanley, E. R., & Pestell, R. G. (2003). Cyclin D1 governs adhesion and motility of macrophages. Molecular biology of the cell, 14(5), 2005-2015. https://doi.org/10.1091/mbc.02-07-0102