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.
Copyright 2002 Wiley-Liss, Inc.