Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer
Gerhard Hamilton1, Barbara Rath1, Lukas Klameth1, Maximilian Hochmair2
1 Ludwig Boltzmann Cluster of Translational Oncology, Vienna, Austria
2 Respiratory Oncology Unit, Otto Wagner Spital, Vienna, Austria
Gerhard Hamilton, email:
Keywords: Small Cell Lung Cancer, Circulating Tumor Cells, Receptor Tyrosine Kinases, Cancer Stem Cells, WNT Pathway
Received: April 17, 2015 Accepted: July 25, 2015 Published: July 31, 2015
Small cell lung cancer (SCLC) has a poor prognosis and is found disseminated at first presentation in the majority of cases. The cell biological mechanisms underlying metastasis and drug resistance is not clear. SCLC is characterized by high numbers of circulating tumor cells (CTCs) and we were able to expand several CTC lines ex vivo and to relate chitinase-3-like-1/YKL-40 (CHI3L1) as marker. Availability of expanded SCLC CTC cells allowed for a screening of receptor tyrosine kinase (RTKs) expressed. The metastatic CHI3L1-negative SCLC cell line SCLC26A, established from a pleural effusion was used for comparison. The CTC cell line BHGc10 was found to exhibit increased expression of RYK, AXL, Tie-1, Dtk, ROR1/2, several ephrins (Eph) and FGF and EGF receptors compared to SCLC26A. All of these RTKs have been associated with cell motility, invasion and poor prognosis in diverse cancer entities without knowledge of their association with CTCs. The identification of RYK, AXL and ROR1/2 as pseudokinases, lacking activity, seems to be related to the observed failure of RTK inhibitors in SCLC. These kinases are involved in the noncanonical WNT pathway and expression in SCLC CTCs represents a cancer stem cell-like phenotype.