Characterization of metastasis formation and virotherapy in the human C33A cervical cancer model

人类 C33A 宫颈癌模型中转移形成和病毒治疗的特征

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作者:Ulrike Donat, Juliane Rother, Simon Schäfer, Michael Hess, Barbara Härtl, Christina Kober, Johanna Langbein-Laugwitz, Jochen Stritzker, Nanhai G Chen, Richard J Aguilar, Stephanie Weibel, Aladar A Szalay

Abstract

More than 90% of cancer mortalities are due to cancer that has metastasized. Therefore, it is crucial to intensify research on metastasis formation and therapy. Here, we describe for the first time the metastasizing ability of the human cervical cancer cell line C33A in athymic nude mice after subcutaneous implantation of tumor cells. In this model, we demonstrated a steady progression of lumbar and renal lymph node metastases during tumor development. Besides predominantly occurring lymphatic metastases, we visualized the formation of hematogenous metastases utilizing red fluorescent protein (RFP) expressing C33A-RFP cells. RFP positive cancer cells were found migrating in blood vessels and forming micrometastases in lungs of tumor-bearing mice. Next, we set out to analyze the influence of oncolytic virotherapy in the C33A-RFP model and demonstrated an efficient virus-mediated reduction of tumor size and metastatic burden. These results suggest the C33A-RFP cervical cancer model as a new platform to analyze cancer metastases as well as to test novel treatment options to combat metastases.

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