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Mosaic Tumor Vessels: Cellular Basis and Ultrastructure of Focal Regions Lacking Endothelial Cell Markers

Steele Laboratory for Tumor Biology, Departments of ¹ Radiation Oncology and ² Anesthesia and Critical Care, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts; and ³ Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, University of California San Francisco, San Francisco, California

Requests for reprints: Lance L. Munn, Department of Radiation Oncology, Harvard Medical School and Massachusetts General Hospital, 100 Blossom Street, Cox-7, Boston, MA 02114. Phone: 617-726-4085; Fax: 617-726-1962; E-mail: lance{at}steele.mgh.harvard.edu.

Endothelial cells of blood vessels in tumors may be thin, fragile, and defective in barrier function. We found previously that the endothelium of vessels in human colon carcinoma xenografts in mice is a mosaic structure. Approximately 85% of tumor vessels have uniform CD31 and/or CD105 immunoreactivity, but the remainder have focal regions that lack these common endothelial markers. The present study assessed the ultrastructure of the vessel lining and the integrity of the basement membrane in these regions. Using immunolabeling and confocal microscopy, we identified blood vessels that lacked CD31 and CD105 immunoreactivity and then analyzed the ultrastructure of these vessels by transmission electron microscopy. Eleven percent of vessels in orthotopic tumors and 24% of vessels in ectopic tumors had defects in CD31 and CD105 staining measuring on average 10.8 µm (range, 1-41.2 µm). Ultrastructural studies identified endothelial cells at 92% of CD31- and CD105-negative sites in orthotopic tumors and 70% of the sites in ectopic tumors. Thus, most regions of tumor vessels that lack CD31 and CD105 immunoreactivity represent attenuated endothelial cells with abnormal expression of endothelial cell markers, but some are gaps between endothelial cells. More than 80% of the defects lacked immunoreactivity for multiple basement membrane proteins.

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