Angiogenic profile of soft tissue sarcomas based on analysis of circulating factors and microarray gene expression.
BACKGROUND
Broader understanding of diverse angiogenic pathways in a particular cancer can lead to better utilization of anti-angiogenic therapies. The aim of this study was to develop profiles of angiogenesis-related gene and protein expression for various histologic subtypes of soft tissue sarcomas (STS) growing in different sites.


METHODS
Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin 2 (Ang2), and leptin were determined in 108 patients with primary STS. Gene expression patterns were analyzed in 38 STS samples and 13 normal tissues using oligonucleotide microarrays.


RESULTS
VEGF and bFGF plasma levels were elevated 10-13 fold in STS patients compared to controls. VEGF levels were broadly elevated while bFGF levels were higher in patients with fibrosarcomas and leiomyosarcomas. Ang2 levels correlated with tumor size and were most elevated for tumors located in the trunk, while leptin levels were highest in patients with liposarcomas. Hierarchical clustering of microarray data based on angiogenesis-related gene expression demonstrated that histologic subtypes of STS often shared similar expression patterns, and these patterns were distinctly different from those of normal tissues. Matrix metalloproteinase 2, platelet-derived growth factor receptor, alpha and Notch 4 were among several genes that were up-regulated at least 7-fold in STS.


CONCLUSIONS
STS demonstrate significant heterogeneity in their angiogenic profiles based on size, histologic subtype, and location of tumor growth, which may have implications for anti-angiogenic strategies. Comparison of STS to normal tissues reveals a panel of upregulated genes that may be targets for future therapies.
Yoon
Sam S
SS
Department of Surgery, Massachusetts General Hospital, Division of Surgical Oncology, Harvard Medical School, Boston, Massachusetts, USA.
Segal
Neil H
NH
Park
Peter J
PJ
Detwiller
Kara Y
KY
Fernando
Namali T
NT
Ryeom
Sandra W
SW
Brennan
Murray F
MF
Singer
Samuel
S
D042702:Angiopoietin-2 / Q000097:blood*; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D009389:Neovascularization, Pathologic / Q000097:blood / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D012509:Sarcoma / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
D042702:Angiopoietin-2; D020738:Leptin; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors