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Cancers 2014, 6(1), 459-471; doi:10.3390/cancers6010459
Article

Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts

1,†
, 1,†
, 1
, 1
, 1,2,3
 and 1,4,5,6,*
Received: 23 December 2013; in revised form: 29 January 2014 / Accepted: 11 February 2014 / Published: 26 February 2014
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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.
Keywords: pancreatic cancer; tumor hypoxia; tumor-associated stroma; patient-derived pancreatic xenograft models; pattern recognition software pancreatic cancer; tumor hypoxia; tumor-associated stroma; patient-derived pancreatic xenograft models; pattern recognition software
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Lohse, I.; Lourenco, C.; Ibrahimov, E.; Pintilie, M.; Tsao, M.-S.; Hedley, D.W. Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts. Cancers 2014, 6, 459-471.

AMA Style

Lohse I, Lourenco C, Ibrahimov E, Pintilie M, Tsao M-S, Hedley DW. Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts. Cancers. 2014; 6(1):459-471.

Chicago/Turabian Style

Lohse, Ines; Lourenco, Corey; Ibrahimov, Emin; Pintilie, Melania; Tsao, Ming-Sound; Hedley, David W. 2014. "Assessment of Hypoxia in the Stroma of Patient-Derived Pancreatic Tumor Xenografts." Cancers 6, no. 1: 459-471.



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