Vascular endothelial growth factor and Kaposi's sarcoma cells in human skin grafts.
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.
Department of Lymphoma/Myeloma, Clinical Cancer Prevention, Departments of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. fsamaniego@mdanderson.org
Felipe
F
Samaniego
Daniel
D
Young
Cara
C
Grimes
Vanessa
V
Prospero
Melpo
M
Christofidou-Solomidou
Horace M
HM
DeLisser
Om
O
Prakash
Aysegul A
AA
Sahin
Suizhao
S
Wang
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002455:Cell Division / Q000276:immunology; D002461:Cell Line, Transformed; D016228:Endothelial Growth Factors / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D015658:HIV Infections / Q000378:metabolism; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000276:immunology; D008222:Lymphokines / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D012514:Sarcoma, Kaposi / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D016038:Skin Transplantation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D039302:Integrin alphaVbeta3; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors