A three-dimensional in vitro model of tumor cell intravasation

Seema M. Ehsan, Katrina M. Welch-Reardon, Marian L. Waterman, Christopher C.W. Hughes, Steven George

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

Metastasis is the cause of over 90% of all human cancer deaths. Early steps in the metastatic process include: the formation of new blood vessels, the initiation of epithelial-mesenchymal transition (EMT), and the mobilization of tumor cells into the circulation. There are ongoing efforts to replicate the physiological landscape of human tumor tissue using three-dimensional in vitro culture models; however, few systems are able to capture the full range of authentic, complex in vivo events such as neovascularization and intravasation. Here we introduce the Prevascularized Tumor (PVT) model to investigate early events of solid tumor progression. PVT spheroids are composed of endothelial and tumor cells, and are embedded in a fibrin matrix containing fibroblasts. The PVT model facilitates two mechanisms of vessel formation: robust sprouting angiogenesis into the matrix, and contiguous vascularization within the spheroid. Furthermore, the PVT model enables the intravasation of tumor cells that is enhanced under low oxygen conditions and is also dependent on the key EMT transcription factor Slug. The PVT model provides a significant advance in the mimicry of human tumors in vitro, and may improve investigation and targeting of events in the metastatic process.

Original languageEnglish (US)
Pages (from-to)603-610
Number of pages8
JournalIntegrative Biology (United Kingdom)
Volume6
Issue number6
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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