Raised plasma endostatin levels correlate inversely with breast cancer angiogenesis.
BACKGROUND
Angiogenesis is essential for solid tumors, such as breast cancer, to grow. The effect of surgical removal of breast tumors on plasma endostatin and vascular endothelial growth factor (VEGF) levels was evaluated. Tumor tissues were analyzed for expression of Intratumoral microvessel density (IMVD) and endostatin. The effect of VEGF and endostatin in inducing apoptosis on human liver microvascular endothelial cells (HLMVEC) was investigated.


METHODS
Plasma from healthy volunteers, patients with fibroadenomas and breast cancer patients were assayed for endostatin and VEGF via immunoassay, pre-operatively and four weeks post-operatively. Expression of endostatin in tumor tissue was determined by Western blotting. IMVD was assessed following immunohistochemical staining with anti-CD34 antibody.


RESULTS
Plasma endostatin levels, in breast cancer patients, were significantly elevated (P = 0.015) in the post-operative (60.59 +/- 7.70 etag/ml) compared with the pre-operative group (30.62 +/- 4.54 etag/ml) and with normal age-matched controls (34.97 +/- 3.76 etag/ml). In patients with high pre-operative plasma endostatin value, IMVD was decreased to 20.1 +/- 3.2 counts compared with 41.9 +/- 5.4 counts in those with low pre-operative endostatin value (P = 0.006). Neither plasma endostatin nor VEGF levels correlated with routine clinico-pathological parameters. Endostatin induced endothelial cell apoptosis and modulated the cytoprotective effect of VEGF in HLMVEC survival.


CONCLUSIONS
Plasma endostatin levels are increased in patients following surgical removal of the primary tumor. The decreased IMVD seen in patients with higher endostatin levels may be due to the apoptosis-inducing effect of endostatin on microvascular endothelial cells.
Teh
Swee H
SH
Department of Surgery, Dublin, Ireland.
Hill
Arnold D K
AD
Lee
Adriana W S
AW
Foley
Deirdre
D
Kennedy
Susan
S
Young
Leonie
L
McDermott
Enda
E
O'Higgins
Niall
N
D000328:Adult; D000368:Aged; D001808:Blood Vessels / Q000473:pathology; D001943:Breast Neoplasms / Q000097:blood / Q000098:blood supply* / Q000601:surgery; D016022:Case-Control Studies; D002470:Cell Survival; D019610:Cytoprotection; D043169:Endostatins / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D018226:Fibroadenoma / Q000097:blood / Q000098:blood supply / Q000601:surgery; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects; D008833:Microcirculation; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood*; D011184:Postoperative Period; D011300:Preoperative Care; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000494:pharmacology
D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A