A short-term in vivo model for Merkel Cell Carcinoma.

Vishwanath Kumble Bhat,Jürgen C Becker,Wolfgang Sattler,Corinna Krump,Eva Bernhart,Nassim Ghaffari‐Tabrizi‐Wizsy

doi:10.1111/exd.13529

Vishwanath Kumble Bhat, Jürgen C Becker + Show 4 more

Open Access

https://doi.org/10.1111/exd.13529

Copy DOI

Abstract

In vivo tumor models are essential for studying the biology of cancer, identifying tumor targets and evaluating antitumor drugs. Considering the request for the minimisation of animal experiments and following the “3R”‐rule (“replacement,” “refinement,” “reduction”), it has become crucial to develop alternative experimental models in cancer biology. Several studies have already described the avian chorioallantoic membrane (CAM) model as an alternative to rodents, suitable to investigate growth, progression and metastasis of various types of cancer. In the present work, we grafted three Merkel cell carcinoma (MCC) cell lines onto the avian CAM and monitored tumor growth and development of solid tumor nodules. Morphology of xenograft was characterised histologically and immunohistochemically. Our results demonstrate CAM assay as a useful tool to study MCC pathophysiology.

Highlights

Merkel Cell Carcinoma (MCC) is a rare, highly aggressive neuroendocrine tumor of the skin with poor prognosis that typically occurs in elderly and immunosuppressed patients.[1]
We investigated whether the chorioallantoic membrane (CAM) system is suitable as a short-term in vivo model for MCC to study tumor growth, proliferation and angiogenesis
We here demonstrated that the CAM system can be used as an experimental in vivo tool that reproduces tumor-stroma interaction, angiogenesis and growth in MCC

Summary

Introduction

Merkel Cell Carcinoma (MCC) is a rare, highly aggressive neuroendocrine tumor of the skin with poor prognosis that typically occurs in elderly and immunosuppressed patients.[1] The MCC is characterised by the presence of cytokeratin 20 (CK-20) and neuroendocrine granules. The outcome of immune surveillance suggested viral carcinogenesis, which was demonstrated in the majority of cases.[2] UV radiation exposure is an additional epidemiologic risk factor for MCC.[3] Due to the development of immune checkpoint inhibitors, a new therapeutic window opened for MCC patients.[4,5,6] Recently, treatment with three humanized antibodies, namely avelumab, pembrolizumab and nivolumab targeting PD-L1/PD-1 pathway have shown durable responses in MCC patients, and avelumab has been approved by the FDA for the treatment of advanced MCC.[7] Even though a panel of well characterised MCC cell lines is available,[8,9,10] the use of these cells in 2D culture systems is of limited value for translation into clinical settings. The CAM model is a time-and cost-effective drug screening system that was successfully used to characterise growth, proliferation and metastasis in a number of other cancer entities.[11,12,13]

Objectives

Conclusion