Cyclin D1 governs adhesion and motility of macrophages.
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.
Neumeister
Peter
P
Division of Hormone-dependent Tumor Biology, The Albert Einstein Comprehensive Cancer Center, Bronx, New York 10461, USA.
Pixley
Fiona J
FJ
Xiong
Ying
Y
Xie
Huafeng
H
Wu
Kongming
K
Ashton
Anthony
A
Cammer
Michael
M
Chan
Amanda
A
Symons
Marc
M
Stanley
E Richard
ER
Pestell
Richard G
RG
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002633:Chemotaxis / Q000502:physiology; D019938:Cyclin D1 / Q000172:deficiency / Q000378:metabolism*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice
D019938:Cyclin D1; D016173:Macrophage Colony-Stimulating Factor