Obesity promotes resistance to anti-VEGF therapy in breast cancer by up-regulating IL-6 and potentially FGF-2. (Sci Transl Med. 2018, 10(432). pii: eaag0945)

報告日期: 2018/11/02
報告時間: 16:00/16:50
報告學生: 饒師維
講評老師: 陳珮君
附件下載: 下載[1751-1538016349-1.pdf] 

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

Incio J, Ligibel JA, McManus DT, Suboj P, Jung K, Kawaguchi K, Pinter M, Babykutty S, Chin SM, Vardam TD, Huang Y, Rahbari NN, Roberge S, Wang D, Gomes-Santos IL, Puchner SB, Schlett CL, Hoffmman U, Ancukiewicz M, Tolaney SM, Krop IE, Duda DG, Boucher Y, Fukumura D, Jain RK

Science translational medicine, March, 2018

Speaker:Shih-Wei Jao (饒師維)                  Time:2018/11/02, 16:00-16:50

Commentator:Prof. Pei-Chun Chen (陳珮君老師)  Place:Room 602

Abstract

   Breast cancer is a common cancer that affects about 1.7 million women around the world. It causes nearly 40,000 American deaths every year. Anti-angiogenesis drug (Bevacizumab), a humanized monoclonal antibody targeting the vascular endothelial growth factor A (VEGF-A), is commonly used in the treatment of colorectal, renal cell, and brain cancer. Previous evidences show obesity promotes the resistance to anti-VEGF drug in the clinical study, because the adipose expansion exceeds that of angiogenesis, causing inadequate tissue vascularization and hypoxia. Therefore, this goal of study is to evaluate the impact of obesity on the anti-VEFG therapy. Firstly, breast cancer patients with obese showed higher expression of blood IL-6 and FGF-2 after anti-VEGF therapy. The lean and obese mice fed with either high-fat diet or low-fat diet were implanted with tumor cells during 8 to 10 weeks after diet initiation, followed by anti-VEGF treatment when the size of tumor cells were about 100 -150 mm3. Anti-VEGF therapy did not effectively inhibit tumor growth in obese as compared to lean mice. The tumors from obese mice presented with lower vessel density. In the adipocyte-rich area, tumors displayed an increase in hypoxia, proliferation, and mitosis, with concomitant lower vessel density and necrosis. The tumors grew in adipocyte-rich areas were observed higher expression of IL-6 expression and were co-localized with the markers for hypoxia and myeloid cell. IL-6 inhibition in combination with the anti-VEFG therapy reduced tumor growth, tumor cell proliferation, and the infiltration of CD4+ T cell. FGF-2 inhibition in combination with the anti-VEGF therapy also decreased tumor growth. In conclusion, the study highlights obesity-promoted expression of IL-6 and FGF-2, resulting in the resistance to anti-VEFG therapy.

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