CX3CR1-fractalkine expression regulates cellular mechanisms involved in adhesion, migration, and survival of human prostate cancer cells.
Chemokines and their receptors might be involved in the selection of specific organs by metastatic cancer cells. For instance, the CXCR4-SDF-1alpha pair regulates adhesion and migration of breast as well as prostate cancer cells to metastatic sites. In this study, we present the first evidence for the expression of CX3CR1--the specific receptor for the chemokine fractalkine--by human prostate cancer cells, whereas human bone marrow endothelial cells and differentiated osteoblasts express fractalkine. The adhesion of prostate cancer cells to human bone marrow endothelial cells in flow conditions is significantly reduced by a neutralizing antibody against fractalkine, and they migrate toward a medium conditioned by osteoblasts, which secrete the soluble form of the chemokine. Finally, fractalkine activates the PI3K/Akt survival pathway in human prostate cancer cells.
Shulby
Shannon A
SA
Department of Pharmacology, Drexel University, College of Medicine, 245 North 15th Street, New College Building, Philadelphia, PA 19102, USA.
Dolloff
Nathan G
NG
Stearns
Mark E
ME
Meucci
Olimpia
O
Fatatis
Alessandro
A
D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D017077:Culture Media, Conditioned; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D010006:Osteoblasts / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000502:physiology*; D015398:Signal Transduction
D000073883:CX3C Chemokine Receptor 1; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D017077:Culture Media, Conditioned; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D019707:Receptors, Chemokine; C095235:CX3CR1 protein, human; C515255:CXCL12 protein, human; C494918:AKT1 protein, human