Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumors

Abstract

Tumor blood vessels are thought to contain genetically normal and stable endothelial cells (ECs), unlike tumor cells, which typically display genetic instability. Yet, chromosomal aberration in human tumor-associated ECs (hTECs) in carcinoma has not yet been investigated. Here we isolated TECs from 20 human renal cell carcinomas and analyzed their cytogenetic abnormalities. The degree of aneuploidy was analyzed by fluorescence in situ hybridization using chromosome 7 and chromosome 8 DNA probes in isolated hTECs. In human renal cell carcinomas, 22-58% (median, 33%) of uncultured hTECs were aneuploid, whereas normal ECs were diploid. The mechanisms governing TEC aneuploidy were then studied using mouse TECs (mTECs) isolated from xenografts of human epithelial tumors. To investigate the contribution of progenitor cells to aneuploidy in mTECs, CD133(+) and CD133(-) mTECs were compared for aneuploidy. CD133(+) mTECs showed aneuploidy more frequently than CD133(-) mTECs. This is the first report showing cytogenetic abnormality of hTECs in carcinoma, contrary to traditional belief. Cytogenetic alterations in tumor vessels of carcinoma therefore can occur and may play a significant role in modifying tumor- stromal interactions.

A liposomal delivery system that targets liver endothelial cells based on a new peptide motif present in the ApoB-100 sequence

“…Liver endothelial cells (Liver ECs) were isolated as previously described (Hida et al, 2004, Akino et al, 2009. Briefly, the liver of a female KSN mouse was excised.…”

Size-controlled, dual-ligand modified liposomes that target the tumor vasculature show promise for use in drug-resistant cancer therapy

“…TECs were isolated, as described previously [17][18][19][20][21][22]. In a typical procedure, the TECs were isolated from OS-RC-2 tumors and dermal tissue in tumor-bearing mice using a magnetic cell sorting system (MACS; Milteny Biotec, Tokyo, Japan).…”

Loss of autocrine endothelial-derived VEGF significantly reduces hemangiosarcoma development in conditional p53-deficient mice

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