Cyclin D1Governs Adhesion and Motility of Macrophages

• DOI: 10.1091/mbc.02-07-0102
• Publication Date: 2003-02-25T01:23:11Z
• Authors: 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
• Keywords: Cyclin D; Cyclin A; Cyclin A2; Retinoblastoma protein; Cyclin B

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