Vascular channel formation by human melanoma cells in vivo and in vitro

Vasculogenic mimicry

Andrew J. Maniotis, Robert Folberg, Angela Hess, Elisabeth A. Seftor, Lynn M G Gardner, Jacob Pe'er, Jeffrey M. Trent, Paul S. Meltzer, Mary J C Hendrix

Research output: Contribution to journalArticle

Abstract

Tissue sections from aggressive human intraocular (uveal) and metastatic cutaneous melanomas generally lack evidence of significant necrosis and contain patterned networks of interconnected loops of extracellular matrix. The matrix that forms these loops or networks may be solid or hollow. Red blood cells have been detected within the hollow channel components of this patterned matrix histologically, and these vascular channel networks have been detected in human tumors angiographically. Endothelial cells were not identified within these matrix-embedded channels by light microscopy, by transmission electron microscopy, or by using an immunohistochemical panel of endothelial cell markers (Factor VIII-related antigen, Ulex, CD31, CD34, and KDR[Flk-1]). Highly invasive primary and metastatic human melanoma cells formed patterned solid and hollow matrix channels (seen in tissue sections of aggressive primary and metastatic human melanomas) in three-dimensional cultures containing Matrigel or dilute Type I collagen, without endothelial cells or fibroblasts. These tumor cell-generated patterned channels conducted dye, highlighting looping patterns visualized angiographically in human tumors. Neither normal melanocytes nor poorly invasive melanoma cells generated these patterned channels in vitro under identical culture conditions, even after the addition of conditioned medium from metastatic pattern-forming melanoma cells, soluble growth factors, or regimes of hypoxia. Highly invasive and metastatic human melanoma cells, but not poorly invasive melanoma cells, contracted and remodeled floating hydrated gels, providing a biomechanical explanation for the generation of microvessels in vitro, cDNA microarray analysis of highly invasive versus poorly invasive melanoma tumor cells confirmed a genetic reversion to a pluripotent embryonic-like genotype in the highly aggressive melanoma cells. These observations strongly suggest that aggressive melanoma cells may generate vascular channels that facilitate tumor perfusion independent of tumor angiogenesis.

Original languageEnglish (US)
Pages (from-to)739-752
Number of pages14
JournalAmerican Journal of Pathology
Volume155
Issue number3
StatePublished - Sep 1999
Externally publishedYes

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Blood Vessels
Melanoma
Neoplasms
Endothelial Cells
In Vitro Techniques
Ulex
Melanocytes
von Willebrand Factor
Microarray Analysis
Conditioned Culture Medium
Collagen Type I
Microvessels
Oligonucleotide Array Sequence Analysis
Transmission Electron Microscopy
Extracellular Matrix
Microscopy
Intercellular Signaling Peptides and Proteins
Necrosis
Coloring Agents
Perfusion

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Maniotis, A. J., Folberg, R., Hess, A., Seftor, E. A., Gardner, L. M. G., Pe'er, J., ... Hendrix, M. J. C. (1999). Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry. American Journal of Pathology, 155(3), 739-752.

Vascular channel formation by human melanoma cells in vivo and in vitro : Vasculogenic mimicry. / Maniotis, Andrew J.; Folberg, Robert; Hess, Angela; Seftor, Elisabeth A.; Gardner, Lynn M G; Pe'er, Jacob; Trent, Jeffrey M.; Meltzer, Paul S.; Hendrix, Mary J C.

In: American Journal of Pathology, Vol. 155, No. 3, 09.1999, p. 739-752.

Research output: Contribution to journalArticle

Maniotis, AJ, Folberg, R, Hess, A, Seftor, EA, Gardner, LMG, Pe'er, J, Trent, JM, Meltzer, PS & Hendrix, MJC 1999, 'Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry', American Journal of Pathology, vol. 155, no. 3, pp. 739-752.
Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LMG, Pe'er J et al. Vascular channel formation by human melanoma cells in vivo and in vitro: Vasculogenic mimicry. American Journal of Pathology. 1999 Sep;155(3):739-752.
Maniotis, Andrew J. ; Folberg, Robert ; Hess, Angela ; Seftor, Elisabeth A. ; Gardner, Lynn M G ; Pe'er, Jacob ; Trent, Jeffrey M. ; Meltzer, Paul S. ; Hendrix, Mary J C. / Vascular channel formation by human melanoma cells in vivo and in vitro : Vasculogenic mimicry. In: American Journal of Pathology. 1999 ; Vol. 155, No. 3. pp. 739-752.
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