Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells, similar to that found in bone metastatic prostate cancer cells

Abstract

BACKGROUND Progressive prostate cancer typically metastasizes to bone where prostate cancer cells gain an osteoblast-like phenotype and induce osteoblastic metastases through unknown mechanisms. To investigate the biology of prostate cancer skeletal metastases, we compared gene expression between the non-metastatic LNCaP cell line and its derivative cell line C4-2B that metastasizes to bone. METHODS Total RNA from LNCaP and C4-2B cell lines was isolated and used to probe membrane-based gene arrays (Comparison 1). Additionally, LNCaP cells were incubated in the absence or presence of conditioned media (CM) from a human osteoblast-like cell line (HOBIT) and total RNA from these cells was used to probe gene arrays (Comparison 2). Differential expression of genes was confirmed by RT-PCR. RESULTS Of the 1,176 genes screened, 35 were differentially expressed between LNCaP and C4-2B cells (Comparison 1). HOBIT-CM induced differential expression of 30 genes in LNCaP cells (Comparison 2). Interestingly, 19 genes that were differentially expressed in C4-2B vs. LNCaP also displayed a similar expression pattern in LNCaPs grown in HOBIT-CM. These genes are primarily involved in motility, metabolism, signal transduction, tumorigenesis, and apoptosis. CONCLUSIONS These results suggest that osteoblasts produce soluble factors that contribute to the progression of prostate cancer skeletal metastases, including their transition to an osteoblast-like phenotype. Additionally, these data provide targets to explore for further investigations towards defining the biology of skeletal metastases. Prostate 51: 10–20, 2002. © 2002 Wiley-Liss, Inc.