Figure 2. BM-derived endothelial cells are luminally incorporated in tumor neovasculature of both murine and human tumors.

(A) High resolution image of a representative nascent CD31+ blood vessel in LLC tumor (day 6–8) showing a luminally incorporated BM-derived GFP⁺ CD31⁺ VE-cadherin⁺ co-expressing endothelial cell (arrow). The BM-derived endothelial cells had a single nucleus, GFP and CD31 signals were localized to the same individual cell, and VE-cadherin was localized to the endothelial cell junction. Scale bar, 20 µM. L, Lumen (Image courtesy of Nolan et al. Genes and Dev 2007).

(B–D) Analysis of secondary tumors that developed in humans previously transplanted with HSCs from a sex-mismatched donor show that tumor endothelial cells are donor-derived as determined by sex chromosome FISH analysis. C: Blood vessel of a male with colon cancer who had not undergone bone marrow transplantation showing endothelial cells with Y chromosome FISH signal (white arrows). D: Section of a thyroid cancer in a female after male bone marrow transplant. Blood vessel with one endothelial cell showing a Y chromosome FISH signal (white arrow). E: Section of male glossal mucoepidermoid carcinoma after female bone marrow transplant. Endothelial cell with two X chromosome FISH signals (white arrow). A single X chromosome (green arrow) positive endothelial cell is presumably derived from male recipient cells.

Note that yellow arrows point to CD45-positive cells with a Y chromosome signal. Endothelial cells were stained with von Willebrand Factor (red) and leukocytes with anti-CD45 antibody (yellow). (Image from Peters et al. Nature Med. 2005).