Журнал канцерогенеза и мутагенеза

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Mature Bone-Producing Osteoblasts Alter Gene Expression of Metastasis Related Genes in Prostate Cancer Cells

Haakon Skogseth, Marius Dybwad, Arnar Flatberg and Jostein Halgunset

Background: Prostate cancers often metastasize to bone. It is hypothesized that interactions between osteoblasts and cancer cells lead to establishment of prostate cancer skeletal metastasis.
Methods: As a result of co-culture between undifferentiated and differentiated osteoblasts and PC-3 and DU-145 prostate cancer cells, gene expressional changes were determined with microarray technology, both Affymetrix® and Illumina® protocols. Characterization of osteoblast differentiation was performed using alizarin red staining of calcium, saffron staining of collagen fibers and quantitative real-time PCR of differentiation markers (RUNX2, Osteocalcin and Alkaline phosphatase).
Results: The Affymetrix® protocol demonstrated that co-culturing of PC-3 cells with differentiated osteoblasts resulted in significantly more expressional changes in the cancer cells than co-culturing with the undifferentiated osteoblasts. The data generated from the Illumina Beadchip platform on DU-144 cells demonstrate a significant larger differential expression (399 reporters) in co-culture with undifferentiated osteoblast cells compared to the differentiated (35 reporters). Morover, this is in contrast to PC-3 cells where co-culture with differentiated osteoblasts dominates the differential expression with 340 reporters while there are only 11 in the case of undifferentiated. However, the Go-Term “Regulation of caspase” (GO:0043281) was found in common in both Affymetrix® and Illumina® array protocols.

Conclusion: Interactions between prostate cancer cells and mature bone-producing osteoblasts resulted in gene expressional changes that may increase cells’ ability to establish bone metastasis. The potential for inducing expressional changes seems to be crucial dependent of the differentiation status of osteoblasts.