TY - JOUR
T1 - Cyclin D1 governs adhesion and motility of macrophages
AU - Neumeister, Peter
AU - Pixley, Fiona J.
AU - Xiong, Ying
AU - Xie, Huafeng
AU - Wu, Kongming
AU - Ashton, Anthony
AU - Cammer, Michael
AU - Chan, Amanda
AU - Symons, Marc
AU - Stanley, E. Richard
AU - Pestell, Richard G.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.02-07-0102
DO - 10.1091/mbc.02-07-0102
M3 - Article
C2 - 12802071
AN - SCOPUS:12444334543
SN - 1059-1524
VL - 14
SP - 2005
EP - 2015
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 5
ER -