Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines

Yuanyuan Ma; Dongming Liang; Jian Liu; Karol Axcrona; Gunnar Kvalheim; Karl-Erik Giercksky; Jahn M Nesland; Zhenhe Suo

doi:10.1007/s13277-012-0325-3

Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines

Tumour Biol. 2012 Aug;33(4):967-78. doi: 10.1007/s13277-012-0325-3. Epub 2012 Jan 18.

Authors

Yuanyuan Ma¹, Dongming Liang, Jian Liu, Karol Axcrona, Gunnar Kvalheim, Karl-Erik Giercksky, Jahn M Nesland, Zhenhe Suo

Affiliation

¹ Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Ullernchausseen 70, 0310 Oslo, Norway.

Abstract

Bone marrow metastases are formed in the late phases of prostate cancer disease. Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are present in the microenvironment of the bone marrow and play a vital role in cell biology therein. The present study was to investigate the influence of SCF and G-CSF on stem-like properties in prostate cancer cell lines. Upon stimulation with SCF or G-CSF, higher levels of CD117, ABCG2, and CD44 were observed in PC-3 and DU145 cells examined by flow cytometry. Simultaneously, the expressions of Oct3/4 and Nanog were upregulated. Moreover, quantitative real-time PCR verified that the increased Nanog under the stimulations was mostly derived from NANOGP8. In parallel with the increasing expressions of these proteins, higher colony and sphere formation efficiencies were seen in these cells in response to the cytokine stimulations. Furthermore, a synergistic effect of SCF and G-CSF on colony and sphere formations and ABCG2 expression was disclosed. Our results indicate a favorable bone marrow niche for prostate cancer cells where higher levels of cell stemness are maintained at least partly by the cytokines SCF and G-CSF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / metabolism
Cell Line, Tumor
Drug Synergism
Flow Cytometry
Gene Expression Regulation, Neoplastic / drug effects
Granulocyte Colony-Stimulating Factor / pharmacology*
Homeodomain Proteins / genetics
Homeodomain Proteins / metabolism
Humans
Hyaluronan Receptors / metabolism
Immunoblotting
Male
Nanog Homeobox Protein
Neoplasm Proteins / metabolism
Neoplastic Stem Cells / drug effects*
Neoplastic Stem Cells / metabolism
Octamer Transcription Factor-3 / metabolism
Prostatic Neoplasms / genetics
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology
Proto-Oncogene Proteins c-kit / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Spheroids, Cellular / drug effects*
Spheroids, Cellular / metabolism
Stem Cell Factor / pharmacology*
Up-Regulation / drug effects

Substances

ABCG2 protein, human
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters
Homeodomain Proteins
Hyaluronan Receptors
NANOG protein, human
Nanog Homeobox Protein
Neoplasm Proteins
Octamer Transcription Factor-3
POU5F1 protein, human
Stem Cell Factor
Granulocyte Colony-Stimulating Factor
Proto-Oncogene Proteins c-kit