Putative CD133+ melanoma cancer stem cells induce initial angiogenesis in vivo.
Tumor angiogenesis is essential for tumor growth and metastasis, and is regulated by a complex network of various types of cells, chemokines, and stimulating factors. In contrast to sprouting angiogenesis, tumor angiogenesis is also influenced by hypoxia, inflammation, and the attraction of bone-marrow-derived cells. Recently, cancer stem cells have been reported to mimic vascularization by differentiating into endothelial cells and inducing vessel formation. In this study, the influence of cancer stem cells on initial angiogenesis was evaluated for the metastatic melanoma cell line D10. Following flow cytometry, CD133+ and CD133- cells were isolated using magnetic cell separation and different cell fractions were transferred to porcine gelatin sponges, which were implanted into the dorsal skinfold chamber of immunocompromised mice. Angiogenesis was analyzed based on microvessel density over a 10-day period using in vivo fluorescence microscopy, and the results were verified using immunohistology. CD133+ D10 cells showed a significant induction of early angiogenesis in vivo, contrary to CD133- D10 cells, unsorted D10 cells, and negative control. Neovascularization was confirmed by visualizing endothelial cells by immunohistology using an anti-CD31 antibody. Because CD133+ cells are rare in clinical specimens and hardly amenable to functional assays, the D10 cell line provides a suitable model to study the angiogenic potential of putative cancer stem cells and the leukocyte-endothelial cell interaction in the dorsal skinfold chamber in vivo. This cancer stem cell model might be useful in the development and evaluation of therapeutic agents targeting tumors.
['Zimmerer|Rüdiger M|RM|', 'Matthiesen|Peter|P|', 'Kreher|Fritjof|F|', 'Kampmann|Andreas|A|', 'Spalthoff|Simon|S|', 'Jehn|Philipp|P|', 'Bittermann|Gido|G|', 'Gellrich|Nils-Claudius|NC|', 'Tavassol|Frank|F|']
D000071916:AC133 Antigen D000818:Animals D015703:Antigens, CD D045744:Cell Line, Tumor D005260:Female D006023:Glycoproteins D006439:Hemodynamics D006801:Humans D018189:Immunomagnetic Separation D000069416:Intravital Microscopy D008545:Melanoma D051379:Mice D016688:Mice, Inbred NOD D016513:Mice, SCID D008856:Microscopy, Fluorescence D055806:Microvessels D014411:Neoplastic Stem Cells D009389:Neovascularization, Pathologic D010455:Peptides
CD133 Melanoma Cancer stem cells Angiogenesis Dorsal skinfold chamber In vivo fluorescence microscopy