Author:
Neumeister Peter,Pixley Fiona J.,Xiong Ying,Xie Huafeng,Wu Kongming,Ashton Anthony,Cammer Michael,Chan Amanda,Symons Marc,Stanley E. Richard,Pestell Richard G.
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, cytokine-mediated chemotaxis, and transendothelial cell migration of cyclin D1-/-bone marrow-derived 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.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
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