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

PLoS One. 2014 Jun 2;9(6):e98533. doi: 10.1371/journal.pone.0098533. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Line, Tumor
  • Female
  • Humans
  • Lymphatic Metastasis
  • Mice
  • Microscopy, Fluorescence
  • Models, Biological*
  • Neoplasm Metastasis*
  • Oncolytic Virotherapy*
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / therapy

Grants and funding

This work was supported by the Research and Development Division of Genelux Corporation, San Diego, USA, and a Service Grant to the University of Wuerzburg, Germany funded by Genelux Corp. UD and SW received postdoctoral fellowship. JR, CK, SS, and MH received a graduate fellowship from Genelux Corporation awarded to the University of Wuerzburg. AAS, JS, NGC, and RJA are salaried employees of Genelux Corporation and have financial interests in Genelux Corporation. BH is a salaried employee of Genelux GmbH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.