American Association for Cancer Research
15357163mct150963-sup-159079_2_supp_3566570_l9nbpl.ppt (3.19 MB)

Supplementary Figures and Tables from Hypoxia-Driven Mechanism of Vemurafenib Resistance in Melanoma

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posted on 2023-04-03, 14:48 authored by Yong Qin, Jason Roszik, Chandrani Chattopadhyay, Yuuri Hashimoto, Chengwen Liu, Zachary A. Cooper, Jennifer A. Wargo, Patrick Hwu, Suhendan Ekmekcioglu, Elizabeth A. Grimm

Figure S1. Chemical Structure of MSC2156119J (Tepotinib, EMD 1214063); Figure S2. Morphology of melanoma cell 2D ambient air cultures and spheroids; Figure S3. The immunofluorescent staining of DAPI and LOX-1 in A375 2D ambient air cultures; Figure S4. The immunofluorescent staining of LOX-1 in MEL1617 3D spheroids on day 3 and 8 of cultures; Figure S5. The human phospho-kinase antibody array of 451Lu spheroids and 2D ambient air cultures; Figure S6. The human phospho-kinase antibody array of A375 spheroids and 2D ambient air cultures; Figure S7. Effect of PLX4032 on BRAF-ERK pathway in melanoma cells under hypoxic conditions. Supplementary Table S1: Primers for RT-PCR and Real-time PCR; Supplementary Table S2: Patient Characteristics; Supplementary Table S3: List of cutaneous melanoma cell lines in CCLE project


UT MD Anderson Cancer Center SPORE


AIM at Melanoma Foundation

Miriam & Jim Mulva Research Funds

Dr. Miriam & Sheldon G. Adelson Medical Research Foundation




Melanoma is molecularly and structurally heterogeneous, with some tumor cells existing under hypoxic conditions. Our cell growth assays showed that under controlled hypoxic conditions, BRAF(V600E) melanoma cells rapidly became resistant to vemurafenib. By employing both a three-dimensional (3D) spheroid model and a two-dimensional (2D) hypoxic culture system to model hypoxia in vivo, we identified upregulation of HGF/MET signaling as a major mechanism associated with vemurafenib resistance as compared with 2D standard tissue culture in ambient air. We further confirmed that the upregulation of HGF/MET signaling was evident in drug-resistant melanoma patient tissues and mouse xenografts. Pharmacologic inhibition of the c-Met/Akt pathway restored the sensitivity of melanoma spheroids or 2D hypoxic cultures to vemurafenib. Mol Cancer Ther; 15(10); 2442–54. ©2016 AACR.

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