Increased drug resistance in breast cancer by tumor-associated macrophages through IL-10/STAT3/bcl-2 signaling pathway

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• 作者：Cuixia Yang (1) (2)
  Linyan He (1) (3)
  Pingqing He (4)
  Yiwen Liu (1)
  Wenjuan Wang (2)
  Yiqing He (1)
  Yan Du (1)
  Feng Gao (1) (2)
  
  1. Department of Molecular Biology Laboratory ; Shanghai Sixth People鈥檚 Hospital ; Shanghai Jiaotong University ; Shanghai ; 200233 ; China
  2. Department of Clinical Laboratory ; Shanghai Sixth People鈥檚 Hospital ; Shanghai Jiaotong University ; Shanghai ; 200233 ; China
  3. Jiangsu Institute of Hematology ; Key Laboratory of Thrombosis and Hemostasis of Ministry of Health ; The First Affiliated Hospital of Soochow University ; Suzhou ; China
  4. Department of Breast Surgery ; Shanghai Sixth People鈥檚 Hospital ; Shanghai Jiaotong University ; Shanghai ; 200233 ; China
  
• 关键词：Tumor ; associated macrophages ; Breast cancer ; Chemoresistance
• 刊名：Medical Oncology
• 出版年：2015
• 出版时间：February 2015
• 年：2015
• 卷：32
• 期：2
• 全文大小：4,865 KB
• 参考文献：1. Mellor AL, Munn DH. Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol. 2008;8:74鈥?0. CrossRef
  2. Solinas G, Germano G, Mantovani A, et al. Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation. J Leukoc Biol. 2009;86:1065鈥?3. CrossRef
  3. Bingle L, Brown NJ, Lewis CE. The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol. 2002;196:254鈥?5. CrossRef
  4. Ojalvo LS, King W, Cox D, et al. High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am J Pathol. 2009;174:1048鈥?4. CrossRef
  5. Mukhtar RA, Nseyo O, Campbell MJ, et al. Tumor-associated macrophages in breast cancer as potential biomarkers for new treatments and diagnostics. Expert Rev Mol Diagn. 2011;11:91鈥?00. CrossRef
  6. De Palma M, Lewis CE. Macrophages limit chemotherapy. Nature. 2011;472:303鈥?. CrossRef
  7. Mantovani A, Sica A, Allavena P, et al. Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation. Hum Immunol. 2009;70:325鈥?0. CrossRef
  8. McMillin DW, Delmore J, Weisberg E, et al. Tumor cell-specific bioluminescence platform to identify stroma-induced changes to anticancer drug activity. Nat Med. 2010;16:483鈥?. CrossRef
  9. Jinushi M, Chiba S, Yoshiyama H, et al. Tumor-associated macrophages regulate tumorigenicity and anticancer drug responses of cancer stem/initiating cells. Proc Natl Acad Sci USA. 2011;108:12425鈥?0. CrossRef
  10. Shree T, Olson OC, Elie BT, et al. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev. 2011;25:2465鈥?9. CrossRef
  11. Sica A, Schioppa T, Mantovani A, et al. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42:717鈥?7. CrossRef
  12. Moore KW, O鈥檊arra A, Malefyt RW, et al. Interleukin-10. Annu Rev Immunol. 1993;11:165鈥?0. CrossRef
  13. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420:860鈥?. CrossRef
  14. Gritsko T, Williams A, Turkson J, et al. Persistent activation of STAT3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res. 2006;12:11鈥?. CrossRef
  15. Alas S, Bonavida B. Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin鈥檚 lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res. 2001;61:5137鈥?4.
  16. Sun Z, Yao Z, Liu S, et al. An oligonucleotide decoy for STAT3 activates the immune response of macrophages to breast cancer. Immunobiology. 2006;211:199鈥?09. CrossRef
  17. Cohen SBA, Crawley JB, Kahan MC, et al. Interleukin-10 rescues T cells from apoptotic cell death: association with an upregulation of Bcl-2. Immunology. 1997;92:1鈥?. CrossRef
  18. Duan Z, Foster R, Bell DA, et al. Signal transducers and activators of transcription 3 pathway activation in drug-resistant ovarian cancer. Clin Cancer Res. 2006;12:5055鈥?3. CrossRef
  19. M眉llauer L, Gruber P, Sebinger D, et al. Mutations in apoptosis genes: a pathogenetic factor for human disease. Mutat Res/Rev Mutat Res. 2001;488:211鈥?1. CrossRef
  20. Mantovani A, Schioppa T, Porta C, et al. Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev. 2006;25:315鈥?2. CrossRef
  21. Tjiu JW, Chen JS, Shun CT, et al. Tumor-associated macrophage-induced invasion and angiogenesis of human basal cell carcinoma cells by cyclooxygenase-2 induction. J Invest Dermatol. 2008;129:1016鈥?5. CrossRef
  22. Yang C, Cao M, Liu H, et al. The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering. J Biol Chem. 2012;287:43094鈥?07. CrossRef
  23. Moore KW, de Waal Malefyt R, Coffman RL, et al. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;9:683鈥?65. CrossRef
  24. Vega MI, Huerta-Yepaz S, Garban H, et al. Rituximab inhibits p38 MAPK activity in 2F7 B NHL and decreases IL-10 transcription: pivotal role of p38 MAPK in drug resistance. Oncogene. 2004;23:3530鈥?0. CrossRef
  25. Komohara Y, Horlad H, Ohnishi K, et al. Importance of direct macrophage鈥搕umor cell interaction on progression of human glioma. Cancer Sci. 2012;103:2165鈥?2. CrossRef
  
• 刊物主题：Oncology; Hematology; Pathology; Internal Medicine;
• 出版者：Springer US
• ISSN：1559-131X

文摘

Tumor-associated macrophages (TAMs) appear to be the major component in solid tumor microenvironment, which were reported to play an important role in tumor malignant progression. Recently, TAMs were reported to be associated with drug resistance in some types of solid tumor including breast cancer. However, how TAMs regulate breast tumor resistance remains unknown. In this study, THP-1 cells were stimulated with PMA and IL-4/IL-13 to form M2-like macrophages to study the role of TAMs on chemoresistance. Our results showed that TAMs and its supernatants significantly prevent breast tumor cells from apoptosis caused by paclitaxel. We also found that the high level of IL-10 secreted by TAMS was responsible for drug resistance of breast cancer. The possible TAMs-modulated drug resistance mechanism involved may be associated with elevation of bcl-2 gene expression and up-regulation of STAT3 signaling in tumor cells. Furthermore, the blockage of TAMs-derived IL-10 by neutralizing antibody resulted in attenuation of STAT3 activation and decrease of bcl-2 mRNA expression, consequently enhanced sensitivity of breast cancer cells. Our data suggested that TAMs might induce drug resistance through IL-10/STAT3/bcl-2 signaling pathway, providing possible new targets for breast tumor therapy.