A more recent version of this article appeared on October 12, 2001

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© 2001 American Heart Association, Inc.

Article

Vascular Morphogenesis and Remodeling in a Human Tumor Xenograft

Blood Vessel Formation and Growth After Ovariectomy and Tumor Implantation

Sybill Patan, Shigeru Tanda, Sylvie Roberge, Rosemary C. Jones, Rakesh K. Jain Lance L. Munn

From the Departments of Radiation Oncology (S.P., L.L.M., S.T., S.R., R.K.J.) and Anesthesia (R.C.J.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass.

Correspondence to Dr S. Patan, Department of Cardiology, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Ave, Bronx, NY 10461. E-mail spatan{at}aecom.yu.edu

Abstract — To determine mechanisms of blood vessel formation and growth in solid tumors, we used a model in which LS174T human colon adenocarcinomas are grown in the isolated ovarian pedicle of nude mice. Reconstruction of 3500 histological serial sections demonstrated that a new vascular network composed of venous-venous loops of varying sizes grows inside the tumor from the wall of the adjacent main vein. Loops elongate and remodel to establish complex loop systems. The mechanisms of loop formation and remodeling correspond to intussusceptive microvascular growth (IMG). In the tissue surrounding the tumor segmentation, another mechanism of IMG is prevalent in venous vessels. Comparison to vascular morphogenesis in the ovariectomized pedicle not only confirms the existence of corresponding mechanisms in both systems, but also reveals numerous sprouts that are superimposed onto loop systems and pathological deviations of loop formation, remodeling, and segmentation in the tumor. These pathological mechanisms interfere with vessel patency that likely cause heterogenous perfusion and hypoxia thus perpetuating angiogenesis. Blood vessel formation based on IMG was also detected in a large thrombus that completely occluded a part of an ovarian artery branch.

Key Words: angiogenesis • colon adenocarcinoma (LS174T) • endothelial cell • intussusceptive microvascular growth • restenosis

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