Open Access Research

Origin of the vasculature supporting growth of primary patient tumor xenografts

Bonnie L Hylander1*, Natalie Punt1, Haikuo Tang14, Joanna Hillman2, Mary Vaughan3, Wiam Bshara3, Rose Pitoniak1 and Elizabeth A Repasky1*

Author Affiliations

1 Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

2 Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

3 Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

4 Current address: Department of Oral and Maxillofacial Surgery, the Affiliated Stomatology Hospital of Sun Yat-sen University, Guangzhou, Guangdong, 510055, China

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Journal of Translational Medicine 2013, 11:110  doi:10.1186/1479-5876-11-110

Published: 3 May 2013

Abstract

Background

Studies of primary patient tumor xenografts grown in immunodeficient mice have shown that these tumors histologically and genetically closely resemble the original tumors. These patient xenograft models are becoming widely used for therapeutic efficacy studies. Because many therapies are directed at tumor stromal components and because the tumor microenvironment also is known to influence the response of a tumor to therapy, it is important to understand the nature of the stroma and, in particular, the vascular supply of patient xenografts.

Methods

Patient tumor xenografts were established by implanting undisrupted pieces of patient tumors in SCID mice. For this study, formalin fixed, paraffin embedded specimens from several types of solid tumors were selected and, using species-specific antibodies which react with formalin fixed antigens, we analyzed the species origin of the stroma and blood vessels that supported tumor growth in these models. Additionally, we investigated the kinetics of the vascularization process in a colon tumor and a mesothelioma xenograft. In mice bearing a head and neck xenograft, a perfusion study was performed to compare the functionality of the human and mouse tumor vessels.

Results

In patient tumors which successfully engrafted, the human stroma and vessels which were engrafted as part of the original tumor did not survive and were no longer detectable at the time of first passage (15–25 weeks). Uniformly, the stroma and vessels supporting the growth of these tumors were of murine origin. The results of the kinetic studies showed that the loss of the human vessels and vascularization by host vessels occurred more rapidly in a colon tumor (by 3 weeks) than in a mesothelioma (by 9 weeks). Finally, the perfusion studies revealed that while mouse vessels in the periphery of the tumor were perfused, those in the central regions were rarely perfused. No vessels of human origin were detected in this model.

Conclusions

In the tumors we investigated, we found no evidence that the human stromal cells and vessels contained in the original implant either survived or contributed in any substantive way to the growth of these xenografts.

Keywords:
Patient tumor xenograft; Vascularization; Primary xenograft