CD74 and CD44 Expression on CTCs in Cancer Patients with Brain Metastasis.

Desirée Loreth ,Harriet Wikman,Klaus Pantel,Beate Volkmer,Christoffer Gebhardt,Jakob Matschke,Manfred Westphal,Melanie Janning,Julia Stadler,Volkmar Müller,Andras Piffko,Iwona Belczacka,Svenja Schneegans,Stefan W Schneider,Jenny Zinke,Sonja Loges,Malte Mohme,Markus Glatzel,Katrin Lamszus,Rüdiger Greinert,Simon A Joosse,Patrick N Harter,M Schuette ,Marie–Laure Yaspo

doi:10.3390/ijms22136993

Abstract

Up to 40% of advance lung, melanoma and breast cancer patients suffer from brain metastases (BM) with increasing incidence. Here, we assessed whether circulating tumor cells (CTCs) in peripheral blood can serve as a disease surrogate, focusing on CD44 and CD74 expression as prognostic markers for BM. We show that a size-based microfluidic approach in combination with a semi-automated cell recognition system are well suited for CTC detection in BM patients and allow further characterization of tumor cells potentially derived from BM. CTCs were found in 50% (7/14) of breast cancer, 50% (9/18) of non-small cell lung cancer (NSCLC) and 36% (4/11) of melanoma patients. The next-generation sequencing (NGS) analysis of nine single CTCs from one breast cancer patient revealed three different CNV profile groups as well as a resistance causing ERS1 mutation. CD44 and CD74 were expressed on most CTCs and their expression was strongly correlated, whereas matched breast cancer BM tissues were much less frequently expressing CD44 and CD74 (negative in 46% and 54%, respectively). Thus, plasticity of CD44 and CD74 expression during trafficking of CTCs in the circulation might be the result of adaptation strategies.

Highlights

The incidence of brain metastases (BM) in many tumor entities has been increasing in the last few decades [1]
circulating tumor cells (CTCs) enrichment from BM patients is challenging as most CTCs shed by BM have been enrichment from BM phenotype, patients is including challenging as most
Show that using marker-independent device, CTCs can be found beenweshown to be of a microfluidic more mesenchymal phenotype, including negative for EpCA

Summary

Introduction

The incidence of brain metastases (BM) in many tumor entities has been increasing in the last few decades [1]. This is attributed to improvements in systemic therapy that are obviously lacking efficacy in the brain. Microfluidic devices using size-based CTC enrichment platforms might be more suitable for the detection of CTCs in BM patients. Further characterization of these CTCs might help in identifying patients prone to develop BM

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Conclusion