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Carcinogenesis Advance Access originally published online on February 20, 2009
Carcinogenesis 2009 30(4):698-705; doi:10.1093/carcin/bgp043
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Prostate stromal cells produce CXCL-1, CXCL-2, CXCL-3 and IL-8 in response to epithelia-secreted IL-1

Ira Kogan-Sakin{dagger}, Merav Cohen{dagger}, Nicole Paland, Shalom Madar, Hilla Solomon, Alina Molchadsky, Ran Brosh, Yosef Buganim, Naomi Goldfinger, Helmut Klocker1, Jack A. Schalken2 and Varda Rotter*

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel
1 Department of Urology, Innsbruck Medical University, A-6020 Innsbruck, Austria
2 Department of Urology, Radboud University Nijmegen Medical Centre 6500 HB, Nijmegen, The Netherlands

* To whom correspondence should be addressed. Tel: +972 8 9344070; Fax: +972 8 9465265; Email: varda.rotter{at}weizmann.ac.il

It is well accepted that tumor microenvironment is essential for tumor cells survival, cancer progression and metastasis. However, the mechanisms by which tumor cells interact with their surrounding at early stages of cancer development are largely unidentified. The aim of this study was to identify specific molecules involved in stromal–epithelial interactions that might contribute to early stages of prostate tumor formation. Here, we show that conditioned medium (CM) from immortalized non-transformed prostate epithelial cells stimulated immortalized prostate stromal cells to express cancer-related molecules. CM obtained from epithelial cells triggered stromal cells to express and secrete CXCL-1, CXCL-2, CXCL-3 and interleukin (IL)-8 chemokines. This effect was predominantly mediated by the cytokines of the IL-1 family secreted by the epithelial cells. Thus, prostate epithelial cells induced the secretion of proinflammatory and cancer-promoting chemokines by prostate stromal cells. Such interactions might contribute to prostatic inflammation and progression at early stages of prostate cancer formation.

Abbreviations: CM, conditioned media; ELISA, enzyme-linked immunosorbent assay; hTERT, human telomerase reverse transcriptase; IL, interleukin; IL-1Ra, interleukin-1 receptor antagonist; mRNA, messenger RNA; NF-{kappa}B, nuclear factor-kappa B; QRT-PCR, quantitative real-time polymerase chain reaction

{dagger} These authors contributed equally to this work.

Received September 4, 2008; revised January 21, 2009; accepted February 6, 2009.


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