Identification of a unique set of genes altered during cell-cell contact in an in vitro model of prostate cancer bone metastasis.
The interaction between prostate cancer cells and bone marrow stromal cells (BMSC) is critical for survival and proliferation of metastatic cancer cells in the bone microenvironment. In order to study molecular mechanisms of prostate cancer bone metastasis, we established a novel heterotypic co-culture system, in which the role of direct cell-cell contact between prostate cancer cells and BMSC in addition to soluble factors can be analyzed. Using both bi-compartmental (insert) system and heterotypic (contact) system, we identified gene expression profiles of interaction between prostate cancer and bone cells. Analysis of differential gene expressions in these two co-culture systems revealed three distinctive sets of genes: 1) genes that were modified only by soluble factors; 2) genes that were regulated by both soluble factors and physical contact; and 3) genes that were altered only by physical contact. The last group consisted of specific set of genes including collagen III, IV, X, XII, integrin alpha1, alpha2, MMP-2, MMP-9, uPA, biglycan, osteopontin and raf-1 in PC3, and collagen VIII, IX, BMP6, TGFbeta1, Smad6 and Twist in BMSC. Among genes that were modified by both soluble factors and physical contact, the gene expression was affected in the same direction (such as MKK4) or in the opposite direction (such as TGFbeta receptor 3). Overall, this suggests that heterotypic cell-cell contact may act as an independent factor affecting the progression of bone metastasis.
Wang
Jun
J
Department of Orthopaedic Surgery, and Robert H. Lurie Comprehensive Cancer Center, The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Levenson
Anait S
AS
Satcher
Robert L
RL
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism