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Open Access 01-06-2009 | Research Paper

Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling

Authors: Åse Bratland, Piet J. Boender, Hanne K. Høifødt, Ingrid H. G. Østensen, Rob Ruijtenbeek, Meng-yu Wang, Jens P. Berg, Wolfgang Lilleby, Øystein Fodstad, Anne Hansen Ree

Published in: Clinical & Experimental Metastasis | Issue 5/2009

Abstract

Bone metastases in prostate cancer are predominantly osteoblastic. To study regulatory mechanisms underlying the establishment of prostate cancer within an osteoblastic microenvironment, human androgen-sensitive prostate carcinoma cells (LNCaP) were treated with culture medium conditioned by human osteoblast-derived sarcoma cells (OHS), and activated signalling pathways in the carcinoma cells were analyzed using microarrays with tyrosine kinase substrates. Network interaction analysis of substrates with significantly increased phosphorylation levels revealed that signalling pathways mediated by EGFR and ERBB2 were activated in LNCaP cells under OHS influence but also by androgen treatment. Activation of EGFR/ERBB2 signalling was also found in LNCaP cells in cocultures with OHS cells or osteoblastic cells that had been differentiated from human mesenchymal stem cells. Our experimental data suggests osteoblast-directed induction of signalling activity via EGFR and ERBB2 in prostate carcinoma cells and may provide a rationale for the use of EGFR or ERBB2 inhibition in systemic prevention or treatment of metastatic prostate cancer in the androgen-sensitive stage of the disease.

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Title: Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling
Authors: Åse Bratland
Piet J. Boender
Hanne K. Høifødt
Ingrid H. G. Østensen
Rob Ruijtenbeek
Meng-yu Wang
Jens P. Berg
Wolfgang Lilleby
Øystein Fodstad
Anne Hansen Ree
Publication date: 01-06-2009
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 5/2009
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-009-9248-9

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