Supplementary Materials

Supplementary Material for:

Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2

Joao Incio, Jennifer A. Ligibel, Daniel T. McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M. Chin, Trupti D. Vardam, Yuhui Huang, Nuh N. Rahbari, Sylvie Roberge, Dannie Wang, Igor L. Gomes-Santos, Stefan B. Puchner, Christopher L. Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M. Tolaney, Ian E. Krop, Dan G. Duda, Yves Boucher, Dai Fukumura,* Rakesh K. Jain*

*Corresponding author. Email: jain{at}steele.mgh.harvard.edu (R.K.J.); dai{at}steele.mgh.harvard.edu (D.F.)

Published 14 March 2018, Sci. Transl. Med. 10, eaag0945 (2018)
DOI: 10.1126/scitranslmed.aag0945

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Correlation of VAT and SAT with BMI.
  • Fig. S2. Correlation between plasma IL-6 and VAT at day 70 and presurgery time points.
  • Fig. S3. Correlation between plasma IL-6 and BMI at day 70 and presurgery time points.
  • Fig. S4. Individual curves of data presented in Fig. 2B.
  • Fig. S5. Correlation between obesity and tumor growth.
  • Fig. S6. Early tumor progression in the setting of diet-induced obesity.
  • Fig. S7. Individual curves of data presented in Fig. 2 (D and E).
  • Fig. S8. Tumor progression influenced by BW but not diet.
  • Fig. S9. Association between obesity and expression of the hypoxia marker GLUT-1.
  • Fig. S10. Quantification of Western blot data presented in Fig. 3C.
  • Fig. S11. Detection and location of adipocytes in tumors.
  • Fig. S12. Expression of additional inflammatory and angiogenic markers in tumors from lean and obese mice treated with B20.
  • Fig. S13. Association between obesity and increased concentrations of tumor IL-6.
  • Fig. S14. Additional representative immunofluorescence stains of F4/80 and CA-IX in E0771 tumors.
  • Fig. S15. Decreased concentration of tumor IL-6 after pharmacological or genetic inhibition in anti-VEGF–treated mice.
  • Fig. S16. Individual tumor growth curves of data presented in Fig. 6A.
  • Fig. S17. Additional images of lungs from mice implanted with E0771 tumors.
  • Fig. S18. Similar effects of pharmacological and genetic inhibition of IL-6 on tumor growth in animals treated with anti-VEGF (B20).
  • Fig. S19. No effect on tumor growth after pharmacological or genetic inhibition of IL-6 alone in obese mice.
  • Fig. S20. Reduced mitotic count with IL-6 inhibition in E0771 tumors from obese mice treated with B20.
  • Fig. S21. Quantification of Western blot data presented in Fig. 6D.
  • Fig. S22. Tumor necrosis induced by B20.
  • Fig. S23. Reduced concentration of tumor CXCL1 in obese mice treated with B20 and IL-6 inhibition.
  • Fig. S24. Expression of additional inflammatory and angiogenic markers in MCaIV tumors from lean and obese mice treated with B20 or obese mice treated with B20 plus metformin.
  • Fig. S25. Association of obesity and increased FGF-2 expression in tumors, particularly around adipocytes and fibroblasts.
  • Fig. S26. CA-IX expression near adipocytes in MCaIV tumors.
  • Fig. S27. Effect of obesity on CA-IX expression in MCaIV tumors.
  • Fig. S28. Individual tumor growth curves of data presented in Fig. 7E.
  • Fig. S29. Decreased BW after FGFR inhibition in tumor-bearing mice treated with B20.
  • Fig. S30. Quantification of Western blot data presented in Fig. 7F.
  • Table S1. Antibodies used for immunohistochemistry.
  • Table S2. Antibodies used for immunofluorescence.
  • Table S3. Antibodies used for Western blotting.
  • Table S4. Antibodies used for flow cytometry.
  • References (8492)

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