Assessment of hypoxia in the stroma of patient-derived pancreatic tumor xenografts

Ines Lohse, Corey Lourenco, Emin Ibrahimov, Melania Pintilie, Ming Sound Tsao, David W. Hedley

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

The unusually dense stroma of pancreatic cancers is thought to play an important role in their biological aggression. The presence of hypoxia is also considered an adverse prognostic factor. Although it is usually assumed that this is the result of effects of hypoxia on the epithelial component, it is possible that hypoxia exerts indirect effects via the tumor stroma. We therefore measured hypoxia in the stroma of a series of primary pancreatic cancer xenografts. Nine patient-derived pancreatic xenografts representing a range of oxygenation levels were labeled by immunohistochemistry for EF5 and analyzed using semi-automated pattern recognition software. Hypoxia in the tumor and stroma was correlated with tumor growth and metastatic potential. The extent of hypoxia varied from 1%-39% between the different models. EF5 labeling in the stroma ranged from 0-20% between models, and was correlated with the level of hypoxia in the tumor cell area, but not microvessel density. Tumor hypoxia correlated with spontaneous metastasis formation with the exception of one hypoxic model that showed disproportionately low levels of hypoxia in the stroma and was non-metastatic. Our results demonstrate that hypoxia exists in the stroma of primary pancreatic cancer xenografts and suggest that stromal hypoxia impacts the metastatic potential.

Original languageEnglish (US)
Pages (from-to)459-471
Number of pages13
JournalCancers
Volume6
Issue number1
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • Pancreatic cancer
  • Patient-derived pancreatic xenograft models
  • Pattern recognition software
  • Tumor hypoxia
  • Tumor-associated stroma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Assessment of hypoxia in the stroma of patient-derived pancreatic tumor xenografts'. Together they form a unique fingerprint.

Cite this