Receptor tyrosine kinase expression of circulating tumor cells in small cell lung cancer.

Gerhard Hamilton,Lukas Klameth,Maximilian Hochmair,Barbara Rath

doi:10.18632/oncoscience.179

Gerhard Hamilton, Lukas Klameth + Show 2 more

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https://doi.org/10.18632/oncoscience.179

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Abstract

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 are 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 kinases (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/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 their expression in SCLC CTCs represents a cancer stem cell-like phenotype.

Highlights

Lung cancer is the leading cause of tumor-associated death worldwide [1]
In the present work we examined the BHGc10 circulating tumor cells (CTCs) line for the presence of one or several receptor tyrosine kinases (RTKs) in consideration of the detection of putative new therapeutic targets
Expression of RTKs was detected on the Western blot arrays for SCLC26A and BHGc10 Small cell lung cancer (SCLC) CTC cells, www.impactjournals.com/oncoscience

Summary

Introduction

Lung cancer is the leading cause of tumor-associated death worldwide [1]. Small cell lung cancer (SCLC) is a neuroendocrine and highly malignant subtype of lung cancer, accounting for approximately 15% of cases, which exhibits a low survival rate at disseminated stage. In contrast to non-small lung cancer (NSCLC), targeted therapy directed to specific oncogenes is not available for SCLC and platinum-based combination chemotherapy with etoposide and second-line topotecan are standard care [2]. So-called liquid biopsies consist of the detection of circulating genetic material or enrichment of the diversified circulating tumor cells (CTCs) using blood samples [5]. SCLC is set apart from other cancers by extremely high number of CTCs in part of the patients [7]. This allowed us for the first time to expand SCLC ex vivo and to set up a few CTC cell lines [8].

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