Pericytes Elicit Resistance to Vemurafenib and Sorafenib Therapy in Thyroid Carcinoma via the TSP-1/TGFβ1 Axis.

ABSTRACT:

Purpose

The BRAF^V600E oncogene modulates the papillary thyroid carcinoma (PTC) microenvironment, in which pericytes are critical regulators of tyrosine-kinase (TK)-dependent signaling pathways. Although BRAF^V600E and TK inhibitors are available, their efficacy as bimodal therapeutic agents in BRAF^V600E-PTC is still unknown.

Experimental design

We assessed the effects of vemurafenib (BRAF^V600E inhibitor) and sorafenib (TKI) as single agents or in combination in BRAF^WT/V600E-PTC and BRAF^WT/WT cells using cell-autonomous, pericyte coculture, and an orthotopic mouse model. We also used BRAF^WT/V600E-PTC and BRAF^WT/WT-PTC clinical samples to identify differentially expressed genes fundamental t

SUBMITTER: Prete A 

PROVIDER: S-EPMC6279578 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature