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RETRACTED ARTICLE: Cancer-associated fibroblasts promote renal cell carcinoma progression

This article was retracted on 20 April 2017

Abstract

The aim of this study was to determine the effect of cancer-associated fibroblasts (CAFs) on renal cell carcinoma (RCC) tumor proliferation, migration, and development of drug resistance, thus underlying their potential as therapeutic targets in RCC patients. CAFs were grown in primary cultures. The in vitro model of interaction of RCC cell lines with CAFs was established. The influence of CAFs on the proliferation and migration ability as well as sensitivity to everolimus of RCC cells was further analyzed. Furthermore, Western blotting analysis was performed to examine the mechanisms mediating the effect of CAFs on RCC cells. The results of the MTT assay showed that coculture with CAFs increased the proliferation activity of both 786-O and Caki-1 cells compared with serum-free medium controls. The migration ability of RCC cell lines was also significantly enhanced after coculture treatment compared with untreated control. The inhibition effect of everolimus on 786-O and Caki-1 cells abrogated in cocultures with CAFs. The sensitivity of both two cell lines to everolimus was dramatically decreased when cocultured with CAFs. RCC cells cocultured with CAFs resulted in the activation of both proliferation-related (Erks) and survival-related (Akt) pathways. These data indicate that CAFs have an important role in supporting and promoting RCC. The interaction of CAFs with RCC cell lines stimulates tumor cell proliferation and migration and induces resistance to everolimus in RCC cells, suggesting that target of the tumor microenvironment may be a novel targeted therapies for RCC.

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References

  1. Ljungberg B, Campbell SC, Choi HY, Jacqmin D, Lee JE, Weikert S, et al. The epidemiology of renal cell carcinoma. Eur Urol. 2011;60(4):615–21.

    Article  PubMed  Google Scholar 

  2. Jonasch E, Futreal A, Davis I, Bailey S, Kim WY, Brugarolas J, et al. State-of-the-science: an update on renal cell carcinoma. Mol Cancer Res. 2012;10(7):859–80.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Janzen NK, Kim HL, Figlin RA. Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am. 2003;30:843–52.

    Article  PubMed  Google Scholar 

  4. Jiang Z, Chu PG, Woda BA, Liu Q, Balaji KC, Rock KL, et al. Combination of quantita-tive IMP3 and tumor stage: a new system to predict metastasis for patients with localized renal cell carcinomas. Clin Cancer Res. 2008;14:5579–84.

    CAS  Article  PubMed  Google Scholar 

  5. Patil S, Ishill N, Deluca J, Motzer RJ. Stage migration and increasing proportion of favor-able-prognosis metastatic renal cell carcinoma patients: implications for clinical trial designand interpretation. Cancer. 2010;116:347–54.

    Article  PubMed  Google Scholar 

  6. Santoni M, Pantano F, Amantini C, Nabissi M, Conti A, Burattini L, et al. Emerging strategies to overcome the resistance to current mTOR inhibitors in renal cell carcinoma. Biochim Biophys Acta. 2014;1845(2):221–31.

    CAS  PubMed  Google Scholar 

  7. Markman B, Dienstmann R, Tabernero J. Targeting the PI3K/Akt/mTOR pathway beyond rapalogs. Oncotarget. 2010;1:530–43.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tlsty T. Cancer: whispering sweet somethings. Nature. 2008;29;453(7195):604–5.

  9. Haubeiss S, Schmid JO, Mürdter TE, Sonnenberg M, Friedel G, van der Kuip H, et al. Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010;9:168.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tlsty TD, Coussens LM. Tumor stroma and regulation of cancer development. Annu Rev Pathol. 2006;1:119–50.

    CAS  Article  PubMed  Google Scholar 

  11. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer. 2006;6(5):392–401.

    CAS  Article  PubMed  Google Scholar 

  12. Hwang RF, Moore T, Arumugam T, Ramachandran V, Amos KD, Rivera A, et al. Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Res. 2008;68(3):918–26.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Hellevik T, Pettersen I, Berg V, Bruun J, Bartnes K, Busund LT, et al. Changes in the secretory profile of NSCLC-associated fibroblasts after ablative radiotherapy: potential impact on angiogenesis and tumor growth. Transl Oncol. 2013;6:66–74.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Allinen M, Beroukhim R, Cai L, et al. Molecular characterization of the tumor microenvironment in breast cancer. Cancer Cell. 2004;6:17–32.

    CAS  Article  PubMed  Google Scholar 

  15. Iacovelli R, Alesini D, Palazzo A, Trenta P, Santoni M, De Marchis L, et al. Targeted therapies and complete responses in first line treatment of metastatic renal cell carcinoma. A meta-analysis of published trials. Cancer Treat Rev. 2014;40(2):271–5.

    CAS  Article  PubMed  Google Scholar 

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Acknowledgments

This study was supported by the grants from the National Natural Science Foundation of China (No. 81472378, No. 81272841, No. 91129725), Shanghai Committee of Science and Technology (13ZR1425100), and National S&T Major Projects (2012ZX09301001-007).

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Correspondence to Jin Zhang or Yiran Huang.

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Yunze Xu and Yongning Lu contributed equally to this work.

The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.

An erratum to this article is available at http://dx.doi.org/10.1007/s13277-017-5487-6.

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Xu, Y., Lu, Y., Song, J. et al. RETRACTED ARTICLE: Cancer-associated fibroblasts promote renal cell carcinoma progression. Tumor Biol. 36, 3483–3488 (2015). https://doi.org/10.1007/s13277-014-2984-8

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  • DOI: https://doi.org/10.1007/s13277-014-2984-8

Keywords

  • Cancer-associated fibroblasts
  • Renal cell carcinoma
  • Everolimus
  • Tumor microenvironment
  • Targeted therapies