Origin of the vasculature supporting growth of primary patient tumor xenografts

Our plain-English summary of Origin of the vasculature supporting growth of primary patient tumor xenografts, by B.L. Hylander, N. Punt, H. Tang, et al (Journal of Translational Medicine, 2013).

The study

• Authors: B.L. Hylander, N. Punt, H. Tang, J. Hillman, M. Vaughan, W. Bshara, R. Pitoniak, E.A. Repasky
• Journal: Journal of Translational Medicine
• Published: 2013;11:110
• Cited by: 63 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

This was a laboratory study in mice. It did not study asbestos exposure, and the article does not mention asbestos; one of the patient tumors used was a mesothelioma of the pleura. The authors implanted small pieces of tumors removed from patients (37 patient tumors in all) under the skin of SCID mice, which are immunodeficient. They then used stains that tell human cells from mouse cells to find where the blood vessels and supporting tissue in the growing tumors came from. In 17 pairs of patient tumors and first-generation mouse tumors, covering 8 tumor types, only the cancer cells in the mouse tumors were human; the supporting tissue was not. In colon, lung, pancreatic and kidney tumors, human vessels were not detectable when the tumors were transferred to new mice. In one patient's mesothelioma, human vessels were still present at 4 weeks but very few remained at 9 weeks. In a colon tumor they were undetectable by 3 weeks. The authors concluded they found no evidence that human vessels contributed significantly to engraftment in the models they examined.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: pieces of patient tumors implanted in SCID mice, analyzed by species-specific immunohistochemistry, with time-course and perfusion studies
• Who was studied: Xenografts in SCID mice derived from 37 patient tumors obtained through the Pathology Resource Network at Roswell Park Cancer Institute (Buffalo, NY). Tumor types included colon, lung, pancreatic, renal cell, head and neck, esophageal, ovarian and duodenal tumors, plus one mesothelioma (pleura, biphasic malignant, from a 70-year-old man who had received radiation and chemotherapy). Study dates were not stated.
• Exposure: No asbestos or fiber exposure was studied. The experimental procedure was implantation of intact pieces of patient tumors into SCID mice.
• Main results:
  • In xenografts that successfully engrafted, the anti-human mitochondrial antibody labeled only the malignant tumor cells; stromal (supporting tissue) cells were not labeled.
  • In first-passage xenografts of colon, lung, pancreatic and renal cell carcinoma, human (huCD31-positive) vessels were not detectable at resection, while mouse (msCD34-positive) vessels were clearly present. Mean time to passage was 15 weeks for colon tumors and 20 to 25 weeks for the other types.
  • In the mesothelioma xenograft, at 4 weeks the human-vessel microvessel density was 15 and the mouse-vessel microvessel density was 44. By 9 weeks very few human vessels were detectable.
  • In the colon tumor xenograft, by 3 weeks after implantation the growing tumor glands were surrounded by mouse vessels and human vessels were not detectable.
  • In head and neck xenografts, perfused vessels were sparse within the tumors. Those detected were of mouse origin, and no vessels labeled for human CD34.
• The authors' conclusion: The authors concluded that they found no evidence that human vessels contribute significantly to engraftment in the models they examined, and that tumor growth was supported by vessels recruited from the mouse host.
• Limitations the authors state:
  • The authors stated that stromal and vascular development should be validated for each individual experimental tumor model, since their findings applied to the tumors they investigated.

Topics

Medical terms in this study, explained in our Lexicon: Tumor Microenvironment, Mesothelioma.

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