Serum endostatin levels are elevated in patients with soft tissue sarcoma

Abstract

BACKGROUND Solid tumors are angiogenesis dependent, and elevated levels of proangiogenic cytokines have been reported in a variety of histologies. Endostatin is an antiangiogenic fragment of the basement membrane protein, collagen XVIII. Because antiangiogenic protein fragments may be generated by tumor‐derived proteases, the authors sought to determine whether circulating levels of endostatin were elevated in patients with localized soft tissue sarcoma. METHODS The authors analyzed preoperative serum levels of endostatin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF) in 25 patients (14 males and 11 females; mean age, 44 years) with soft tissue sarcoma. For each serum sample, two aliquots were assayed in duplicate using a competitive enzyme immunoassay. Serum levels were compared with levels from 34 age‐matched and gender‐matched volunteer blood donors. RESULTS Endostatin levels were significantly higher in sera from sarcoma patients than in sera from healthy controls (43.0 ng/mL vs. 25.8 ng/mL, respectively; P = 0.0002; Mann–Whitney U test). Significant elevations also were noted in VEGF and bFGF levels (P = 0.0002 and P = 0.0001, respectively). Furthermore, endostatin levels > 2 standard deviations above the control mean (55 ng/mL) were associated with an increased risk of tumor recurrence after resection (P = 0.047; log‐rank test). CONCLUSIONS Serum endostatin, VEGF, and bFGF levels are elevated in patients with soft tissue sarcoma. Elevated endostatin levels appear to be associated with tumor aggressiveness. The role of these cytokines in sarcoma angiogenesis and as potential targets for therapy warrants further study. Cancer 2001;91:1525–9. © 2001 American Cancer Society.

Autoantibodies to endostatin in patients with breast cancer: correlation to endostatin levels and clinical outcome

“…Another hypothesis to explain this 'paradox' is that elevated serum endostatin mostly reflects ongoing angiogenesis, as it is known that (i) matrix metalloprotease, which is activated during angiogenesis, can cleave collagen and modify its structure (Xu et al, 2001;Hangai et al, 2002), and (ii) collagen XVIII is mainly synthesised in the perivascular basement membrane of tumourassociated blood vessels (Muragaki et al, 1995;St Croix et al, 2000;Guenther et al, 2001). This can explain that large and aggressive tumours will generate more soluble endostatin than small ones (Feldman et al, 2001). Finally, it should be noted that the functional status of the soluble endostatin detected in this study has not been ascertained, similar to other studies using the same competitive EIA (Feldman et al, 2002;Bono et al, 2003).…”

Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma

“…It may seem paradoxical because VEGF is known for its proangiogenesis function while endostatin is an angiogenesis inhibitor. However, cumulative evidences indicate that serum endostatin and VEGF level are concomitantly escalated in many types of cancer 15,[24][25][26][27][28] including HCC. 15 Assuming the serum endostatin levels reflected that in tissues, the correlation between tissue endostatin/ C18 and VEGF level in HCC samples seemed to be consistent with such an observation.…”

Markers of angiogenesis and clinical features in patients with sarcoma

“…21 Five other studies have demonstrated that circulating VEGF levels are significantly elevated in patients with soft-tissue sarcoma. [22][23][24][25][26] Patients with GIST have higher serum VEGF levels than healthy controls. 27 Most studies have reported that elevated circulating VEGF levels correlate with higher tumor grade and increased local disease burden, but not with the presence of metastatic disease.…”

“…22,[24][25][26] Preoperative circulating VEGF levels did not have prognostic significance in the 2 studies evaluating this issue. 23,25 Another study followed serum VEGF levels after surgical or medical therapy for soft-tissue sarcoma and found that rising VEGF levels heralded recurrent or refractory disease. 24 Circulating angiopoietin-2 and basic fibroblast growth factor (bFGF) levels are also elevated in patients with soft-tissue sarcoma compared with healthy controls.…”