Differential effects of MAPK pathway inhibitors on migration and invasiveness of BRAF(V600E) mutant thyroid cancer cells in 2D and 3D culture
| Autor: | Camilla Ingeson-Carlsson, Angela Martinez-Monleon, Mikael Nilsson |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Proto-Oncogene Proteins B-raf medicine.medical_specialty Indoles Cell Survival Cell Culture Techniques Antineoplastic Agents Biology Thyroid Carcinoma Anaplastic Cell Movement Internal medicine Cell Line Tumor Nitriles medicine Butadienes Humans Neoplasm Invasiveness Anaplastic thyroid cancer Phosphorylation Thyroid cancer Protein Kinase Inhibitors Tumor microenvironment Sulfonamides Carcinoma Cancer Cell Biology medicine.disease Endocrinology Cell culture Mutation Cancer research Signal transduction Mitogen-Activated Protein Kinases V600E Signal Transduction |
| Zdroj: | Experimental cell research. 338(2) |
| ISSN: | 1090-2422 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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