title: Bone marrow mesenchymal stem cells increase motility of prostate cancer cells via production of stromal cell-derived factor-1α.
abstract: Prostate cancer frequently metastasizes to the bone, and the interaction between cancer cells and bone microenvironment has proven to be crucial in the establishment of new metastases. Bone marrow mesenchymal stem cells (BM-MSCs) secrete various cytokines that can regulate the behaviour of neighbouring cell. However, little is known about the role of BM-MSCs in influencing the migration and the invasion of prostate cancer cells. We hypothesize that the stromal cell-derived factor-1α released by BM-MSCs may play a pivotal role in these processes. To study the interaction between factors secreted by BM-MSCs and prostate cancer cells we established an in vitro model of transwell co-culture of BM-MSCs and prostate cancer cells DU145. Using this model, we have shown that BM-MSCs produce soluble factors which increase the motility of prostate cancer cells DU145. Neutralization of stromal cell-derived factor-1α (SDF1α) via a blocking antibody significantly limits the chemoattractive effect of bone marrow MSCs. Moreover, soluble factors produced by BM-MSCs greatly activate prosurvival kinases, namely AKT and ERK 1/2. We provide further evidence that SDF1α is involved in the interaction between prostate cancer cells and BM-MSCs. Such interaction may play an important role in the migration and the invasion of prostate cancer cells within bone.
authors.affiliation: Department of Clinical and Biological Science, University of Turin, Orbassano, Italy. barbara.mognetti@unito.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Mognetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Montagna
authors.forename: Maria Giulia
authors.initials: MG
authors.lastname: Perrelli
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
authors.forename: Claudia
authors.initials: C
authors.lastname: Penna
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D001596:Benzylamines; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D019380:Anti-HIV Agents; D001596:Benzylamines; D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; D000080027:Cyclams; D006571:Heterocyclic Compounds; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C088327:plerixafor