Vascular endothelial growth factor and Kaposi's sarcoma cells in human skin grafts.

Abstract

Human cancer cells often produce tumors in animal models that incompletely reproduce the histology of the parental tumor. Kaposi's sarcoma (KS) cells, in particular, have not produced durable angiogenic lesions in animal models that resemble those of KS in humans. We investigated the contribution of transformed KS cells, vascular endothelial growth factor (VEGF), and human skin tissue on tumor development in a human skin graft/mouse model. High levels of serum VEGF (322 pg/ml) were seen in HIV-1-infected persons with KS compared with HIV-1-infected persons without KS (115 pg/ml). Human KS lesions expressed VEGF in the spindle cells. Transformed KS cells expressed the mitogenically active 121-amino acid and 165-amino acid isoforms of VEGF. Tumors induced by KS cells implanted in the SCID mice grew preferentially in human skin grafts rather than in ungrafted murine skin. Tumors induced in the presence of human skin grafts developed numerous lumens expressing alpha(v)beta(3) integrin. KS cells inoculated with neutralizing anti-VEGF antibody did not form tumors. This study supports an important role for VEGF in tumor development and shows how a human tissue can preferentially promote tumor growth.

• Authors: Felipe Samaniego, Daniel Young, Cara Grimes, Vanessa Prospero, Melpo Christofidou-Solomidou, Horace M DeLisser, Om Prakash, Aysegul A Sahin, Suizhao Wang
• Journal: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research (Cell Growth Differ) Vol. 13 Issue 8 Pg. 387-95 (Aug 2002) ISSN: 1044-9523 [Print] United States
• PMID: 12193477 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies
• Endothelial Growth Factors
• Integrin alphaVbeta3
• Intercellular Signaling Peptides and Proteins
• Lymphokines
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors

Topics

• Animals
• Antibodies (pharmacology)
• Cell Division (immunology)
• Cell Line, Transformed
• Endothelial Growth Factors (antagonists & inhibitors, blood, immunology)
• Graft Survival (immunology)
• HIV Infections (metabolism)
• HIV-1 (metabolism)
• Humans
• Immunohistochemistry
• Integrin alphaVbeta3 (genetics)
• Intercellular Signaling Peptides and Proteins (blood, immunology)
• Lymphokines (antagonists & inhibitors, blood, immunology)
• Male
• Mice
• Neoplasm Transplantation
• Sarcoma, Kaposi (metabolism, pathology)
• Skin Neoplasms (metabolism, pathology)
• Skin Transplantation
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors