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Differential effects of MAPK pathway inhibitors on migration and invasiveness of BRAF(V600E) mutant thyroid cancer cells in 2D and 3D culture

Journal article
Authors Camilla Ingeson-Carlsson
Angela Martinez-Monleon
Mikael Nilsson
Published in Experimental Cell Research
Volume 338
Issue 2
Pages 127-135
ISSN 0014-4827
Publication year 2015
Published at Sahlgrenska Cancer Center
Institute of Biomedicine
Pages 127-135
Language en
Keywords Thyroid, Cancer, BRAF, MEK, U0126, PLX4720, Migration, 3D, kappa-b activation, braf mutations, constitutive activation, mesenchymal, transition, tumor microenvironment, promotes invasiveness, mek, inhibition, kinase, resistance, carcinoma, Oncology, Cell Biology
Subject categories Cancer and Oncology, Cell biology


Tumor microenvironment influences targeted drug therapy. In this study we compared drug responses to RAF and MEK inhibitors on tumor cell migration in 2D and 3D culture of BRAF(V600E) mutant cell lines derived from human papillary (BCPAP) and anaplastic (SW1736) thyroid carcinomas. Scratch wounding was compared to a double-layered collagen gel model developed for analysis of directed tumor cell invasion during prolonged culture. In BCPAP both PLX4720 and U0126 inhibited growth and migration in 2D and decreased tumor cell survival in 3D. In SW1736 drugs had no effect on migration in 2D but decreased invasion in 3D, however this related to reduced growth. Dual inhibition of BRAF(V600E) and mEK reduced but did not prevent SW1736 invasion although rebound phosphorylation of ERK in response to PLX4720 was blocked by U0126. These findings indicate that anti-tumor drug effects in vitro differ depending on culture conditions (2D vs. 3D) and that the invasive features of anaplastic thyroid cancer depend on non-MEK mechanism(s). (C) 2015 Elsevier Inc. All rights reserved.

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