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
Reference64 articles.
1. Aharinejad, S., Abraham, D., Paulus, P., Abri, H., Hofmann, M., Grosschmidt, K., Schafer, R., Stanley, E.R., and Hofbauer, R. (2002). CSF-1 anti-sense treatment suppresses growth of human tumor xenografts in mice.Cancer Res.62, 5317–5324.
2. Albanese, C.et al. (1999). Activation of thecyclin D1gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis.J. Biol. Chem.274, 34186–34195.
3. Allen, W.E., Jones, G.E., Pollard, J.W., and Ridley, A.J. (1997). Rho, Rac and Cdc42 regulate actin organization and cell adhesion in macrophages.J. Cell Sci.110, 707–720.
4. Allen, W.E., Zicha, D., Ridley, A.J., and Jones, G.E. (1998). A role for cdc42 in macrophage chemotaxis.J. Cell. Biol.141, 1147–1157.
5. Epidermal Growth Factor Receptor Distribution during Chemotactic Responses
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