p65-Dependent production of interleukin-1β by osteolytic prostate cancer cells causes an induction of chemokine expression in osteoblasts.
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p65-Dependent production of interleukin-1β by osteolytic prostate cancer cells causes an induction of chemokine expression in osteoblasts. / Schulze, Jochen; Riecken, Kristoffer; Baranowsky, Anke; Streichert, Thomas; Lange, Tobias; Spiro, Alexander Simon; Albers, Joachim; Seitz, Sebastian; Zustin, Jozef; Amling, Michael; Fehse, Boris; Schinke, Thorsten.
in: CANCER LETT, Jahrgang 317, Nr. 1, 1, 2012, S. 106-113.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - p65-Dependent production of interleukin-1β by osteolytic prostate cancer cells causes an induction of chemokine expression in osteoblasts.
AU - Schulze, Jochen
AU - Riecken, Kristoffer
AU - Baranowsky, Anke
AU - Streichert, Thomas
AU - Lange, Tobias
AU - Spiro, Alexander Simon
AU - Albers, Joachim
AU - Seitz, Sebastian
AU - Zustin, Jozef
AU - Amling, Michael
AU - Fehse, Boris
AU - Schinke, Thorsten
PY - 2012
Y1 - 2012
N2 - Skeletal metastases are a frequent complication of prostate, breast and lung cancer, and the interactions of tumor cells with bone-forming osteoblasts and bone-resorbing osteoclasts have been suggested to play critical roles in disease progression. We have previously shown that treatment of primary murine osteoblasts with conditioned medium of the human osteolytic prostate cancer cell line PC-3 results in a rapid induction of chemokine expression, thereby providing further evidence for a molecular crosstalk between bone and tumor cells. The aim of our current study was to identify PC-3-derived molecules mediating this effect. Using Affymetrix Gene Chip hybridization followed by qRT-PCR we were able to confirm that the expression of chemokine-encoding genes is markedly induced in human primary osteoblasts following incubation with PC-3-conditioned medium. Since this induction was significantly affected upon alteration of p65-levels in PC-3 cells, we performed a second genome-wide expression analysis to identify p65-regulated cytokines, which were then tested for their ability to induce chemokine expression. Here we observed that interleukin-1? (IL-1B) did not only increase the expression of chemokines in osteoblasts, but also the phosphorylation of p65 and thereby its own expression. Since immunohistochemistry on bone biopsy sections from prostate cancer metastases demonstrated IL-1B expression in both, tumor cells and osteoblasts, our data suggest that IL-1B is one of the relevant cytokines involved in the skeletal complications of cancer metastases.
AB - Skeletal metastases are a frequent complication of prostate, breast and lung cancer, and the interactions of tumor cells with bone-forming osteoblasts and bone-resorbing osteoclasts have been suggested to play critical roles in disease progression. We have previously shown that treatment of primary murine osteoblasts with conditioned medium of the human osteolytic prostate cancer cell line PC-3 results in a rapid induction of chemokine expression, thereby providing further evidence for a molecular crosstalk between bone and tumor cells. The aim of our current study was to identify PC-3-derived molecules mediating this effect. Using Affymetrix Gene Chip hybridization followed by qRT-PCR we were able to confirm that the expression of chemokine-encoding genes is markedly induced in human primary osteoblasts following incubation with PC-3-conditioned medium. Since this induction was significantly affected upon alteration of p65-levels in PC-3 cells, we performed a second genome-wide expression analysis to identify p65-regulated cytokines, which were then tested for their ability to induce chemokine expression. Here we observed that interleukin-1? (IL-1B) did not only increase the expression of chemokines in osteoblasts, but also the phosphorylation of p65 and thereby its own expression. Since immunohistochemistry on bone biopsy sections from prostate cancer metastases demonstrated IL-1B expression in both, tumor cells and osteoblasts, our data suggest that IL-1B is one of the relevant cytokines involved in the skeletal complications of cancer metastases.
KW - Humans
KW - Male
KW - Immunohistochemistry
KW - Up-Regulation
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Cell Line, Tumor
KW - Oligonucleotide Array Sequence Analysis
KW - Phosphorylation
KW - Transfection
KW - RNA Interference
KW - Gene Expression Profiling/methods
KW - Bone Neoplasms/genetics/immunology/metabolism/secondary
KW - Chemokines/genetics/metabolism
KW - Culture Media, Conditioned/metabolism
KW - Interleukin-1beta/metabolism
KW - Osteoblasts/immunology/metabolism
KW - Paracrine Communication
KW - Prostatic Neoplasms/genetics/immunology/metabolism/pathology
KW - Transcription Factor RelA/genetics/metabolism
KW - Humans
KW - Male
KW - Immunohistochemistry
KW - Up-Regulation
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Cell Line, Tumor
KW - Oligonucleotide Array Sequence Analysis
KW - Phosphorylation
KW - Transfection
KW - RNA Interference
KW - Gene Expression Profiling/methods
KW - Bone Neoplasms/genetics/immunology/metabolism/secondary
KW - Chemokines/genetics/metabolism
KW - Culture Media, Conditioned/metabolism
KW - Interleukin-1beta/metabolism
KW - Osteoblasts/immunology/metabolism
KW - Paracrine Communication
KW - Prostatic Neoplasms/genetics/immunology/metabolism/pathology
KW - Transcription Factor RelA/genetics/metabolism
M3 - SCORING: Journal article
VL - 317
SP - 106
EP - 113
JO - CANCER LETT
JF - CANCER LETT
SN - 0304-3835
IS - 1
M1 - 1
ER -
