Comparison and modulation of angiogenic responses by FGFs, VEGF and SCF in murine and human fibrosarcomas.
The effects of angiogenic growth factors on the growth, vascular architecture and the downstream cytokine signaling of sarcomas are unknown. These are of potential great importance since sarcoma, like endothelium, is of mesodermal origin and therefore could grow in response to these factors. Three human sarcomas (leiomyosarcoma SK-LMS-1, liposarcoma SW872 and fibrosarcoma SW684) and one murine fibrosarcoma (KHT) were grown in nude and C3H/He mice, respectively. Tumor structural vessels, perfused vessels and hypoxia were quantified immunohistochemically. Fast-growing murine KHT tumors had a markedly higher number of structural vessels compared with the human sarcomas. In both murine and human sarcomas, approximately half of the total structural vessels were perfused, and the numbers of perfused vessels decreased with increasing tumor volume. In vitro, basal mRNA expression of several angiogenic growth factors and their receptors differed between two of the human sarcoma cell lines, SK-LMS-1 and SW872. Compared with SK-LMS-1, untreated SW872 cells had higher levels of mRNA expression for FGF11, FGF14, angiopoietin, CD105 and VEGFR1. Two sarcoma cell lines were also treated with 10 ng/ml of six angiogenic growth factors (FGF1, FGF2, FGF7, FGF10, VEGF and SCF) for 24 h, and mRNA expression of endogenous FGF family members (FGF1, FGF2, FGF10, FGF11, FGF13 and FGF14) were quantitatively measured using RNase protection at various times following treatments. Again, SW872 cells were more responsive to exogenous growth factor treatment compared with SK-LMS-1 cells in terms of the elevation of endogenous FGF mRNA expression. In the SW872 cells, all of the exogenous angiogenic growth factor treatments, except for VEGF, upregulated endogenous FGF1, FGF2 and FGF14 mRNA expression. The SK-LMS-1 cells, in contrast, only responded to exogenous FGF1, FGF7 and FGF10, but did not respond to VEGF.
Ding
Ivan
I
Department of Radiation Oncology, Box 647, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. ivan@radonc.medinfo.rochester.edu
Liu
Weimin
W
Sun
Jianzhong
J
Fenton
Bruce
B
Okunieff
Paul
P
D000818:Animals; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005354:Fibrosarcoma / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D012333:RNA, Messenger; D019089:Stem Cell Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005346:Fibroblast Growth Factors