PTK787/ZK 222584 inhibits tumor growth promoting mesenchymal stem cells: Kinase activity profiling as powerful tool in functional studies

Abstract

Bone marrow (BM)-derived mesenchymal stem cells (MSCs) have been shown to

favour tumor growth, suggesting the relevance of pharmaceutical inhibition of MSCs

for the treatment of malignancies. We tested the effect of PTK787/ZK 222584 (PTK)

on the outgrowth of MSCs from human bone marrow-derived mononuclear cells

(MNCs) and the migration and tube formation capacity of MSCs in vitro. PTK dose-

dependently inhibited the outgrowth of BM-MSCs from BM-MNCs (LC50 1.12 μM

PTK), while hematopoietic colony formation (HCF) was only slightly hampered (13 ±

19% at 1 μM PTK, and stable at ~50% at higher concentrations of PTK). Addition of

10 μM PTK inhibited proliferation of MSCs by 74 ± 6.6% compared to control

(p