RGD Reference Report - Interleukin-6 inhibits the growth of prostate cancer xenografts in mice by the process of neuroendocrine differentiation. - Rat Genome Database

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Interleukin-6 inhibits the growth of prostate cancer xenografts in mice by the process of neuroendocrine differentiation.

Authors: Wang, Q  Horiatis, D  Pinski, J 
Citation: Wang Q, etal., Int J Cancer. 2004 Sep 10;111(4):508-13.
RGD ID: 2293734
Pubmed: PMID:15239127   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.20286   (Journal Full-text)

In vitro, the human prostate cancer (PCA) cell line LNCaP can be permanently transdifferentiated into a quiescent neuroendocrine (NE) phenotype by the cytokine interleukin-6 (IL-6). Recently, we have shown that the growth of prostate cancer cells is significantly suppressed when cocultured with NE cells. In order to explore the inhibitory activity of IL-6 on prostate tumor growth, nude mice bearing xenografts of the PCA cell lines LNCaP and DU-145 (a line that is incapable of NE transdifferentiation by IL-6 in vitro) were treated with IL-6 for 3 weeks, either injected around the tumor or systematically released from implanted minipumps. Both administration forms of IL-6 inhibited the growth of LNCaP xenografts by more than 75% compared to the control group. In contrast, there was no difference in DU-145 tumor growth between IL-6-treated animals and controls. In comparison to control and DU-145 tumors, both IL-6 injected and pump-infused LNCaP tumors exhibited a significant increase in the expression of the NE markers neuron-specific enolase (NSE) and betaIII tubulin. Serum NSE levels were also significantly elevated in both IL-6-treated LNCaP tumor groups when compared to controls. IL-6 treatment resulted in G(0) cell cycle accumulation as evidenced by a loss of Ki-67 expression in > 90% of LNCaP tumor cells. These combined results demonstrate that IL-6-induced NE transdifferentiation of PCA cells has a significant inhibitory effect on tumor growth in mice. Agents, like IL-6, capable of NE transdifferentiation of PCA cells, should be considered as a new therapeutic approach for the treatment of prostate cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
prostate cancer  IMP 2293734 RGD 
prostate cancer  ISOENO2 (Homo sapiens)2293734; 2293734 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Eno2  (enolase 2)

Genes (Mus musculus)
Eno2  (enolase 2, gamma neuronal)

Genes (Homo sapiens)
ENO2  (enolase 2)


Additional Information