Xenograft Models of Herceptin Resistance in Breast Cancer
- سال انتشار: 1394
- محل انتشار: اولین سمپوزیوم بین المللی سرطان نسترن
- کد COI اختصاصی: NASTARANCANSER01_011
- زبان مقاله: انگلیسی
- تعداد مشاهده: 573
نویسندگان
Division of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute ofGenetic Engineering and Biotechnology (NIGEB), Tehran, I.R. Iran
Division of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute ofGenetic Engineering and Biotechnology (NIGEB), Tehran, I.R. Iran
چکیده
Herceptin (Trastuzumab, TZMB) is a humanized monoclonal antibody used to treat HER2+ breastcancer (BC). Patient resistance against TZMB therapyis a major clinical issue to be addressed.Infiltrating fibroblasts secrete glial cell line-derived neurotrophic factor (GDNF) to the tumormicroenvironment. Besides, GDNF receptor RET contributes to hormone resistance in BC bycrosstalking with HER receptors.We hypothesized that GDNF can promote a bypassing mechanism toconfront TZMB resistance by inducing RET-HER2 crosstalks via non-receptor tyrosine kinase SRC.We created animal models of sensitive and resistant human tumors by collecting tumor samples fromthree patients bearing HER2-, HER2+/TZMBSensitive (S)and HER2+/TZMBResistance (R)BC tumors, andinjectingthe samplesinto SCID/nude mice. The generatedtumor models were treated first with TZMBfor 4 weeks and then with TZMB+GDNF for the second 4-week period. Three distinct cell lines wereisolated from these three xenograft models in order to facilitate examination ofpossible mechanismsbehind TZMB resistance. Dose responses were determined based on which tumor cell treatment andco-treatment studies were designed and carried out. Cell survival and apoptosis rates were examined.The sensitive xenograft tumor but not the HER2- or resistant ones shrunk upon treatment withTZMB.In contrast, GDNF induced sensitive tumor growth and effectively prevented TZMB frominducing apoptosis. We are currently using these cell lines to examine if GDNF can confrontTZMBmediatedapoptosis in sensitive tumors and activate alternative growth pathways inBC tumors that arenot responding to TZMB therapy. GDNF potentially abrogates TZMB action on inducing BC cellapoptosis and can activate alternative routes for growth inTZMB-resistant BC cells.Xenograft modelsprovide informative insights into cell-molecular mechanisms behind antibody resistance among BCpatients and hold promise for shapingfuture directionsfor overcoming this clinically critical issue.کلیدواژه ها
مقالات مرتبط جدید
اطلاعات بیشتر در مورد COI
COI مخفف عبارت CIVILICA Object Identifier به معنی شناسه سیویلیکا برای اسناد است. COI کدی است که مطابق محل انتشار، به مقالات کنفرانسها و ژورنالهای داخل کشور به هنگام نمایه سازی بر روی پایگاه استنادی سیویلیکا اختصاص می یابد.
کد COI به مفهوم کد ملی اسناد نمایه شده در سیویلیکا است و کدی یکتا و ثابت است و به همین دلیل همواره قابلیت استناد و پیگیری دارد.