title: Monitoring multiple angiogenesis-related molecules in the blood of cancer patients shows a correlation between VEGF-A and MMP-9 levels before treatment and divergent changes after surgical vs. conservative therapy.
abstract: Anti-angiogenic therapies are currently in cancer clinical trials, but to date there are no established tests for evaluating the angiogenic status of a patient. We measured 11 circulating angiogenesis-associated molecules in cancer patients before and after local treatment. The purpose of our study was to screen for possible relationships among the different molecules and between individual molecules and tumor burden. We measured VEGF-A, PlGF, SCF, MMP-9, EDB+ -fibronectin, sVEGFR-2, sVEGFR-1, salphaVbeta3, sTie-2, IL-8 and CRP in the blood of 22 healthy volunteers, 17 early breast, 17 early colorectal, and 8 advanced sarcoma/melanoma cancer patients. Breast cancer patients had elevated levels of VEGF-A and sTie-2, colorectal cancer patients of VEGF-A, MMP-9, sTie-2, IL-8 and CRP, and melanoma/sarcoma patients of sVEGFR-1. salphaVbeta3 was decreased in colorectal cancer patients. A correlation between VEGF-A and MMP-9 was found. After tumor removal, MMP-9 and salphaVbeta3 significantly decreased in breast and CRP in colorectal cancer, whereas sVEGFR-1 increased in colorectal cancer patients. In sarcoma/melanoma patients treated regionally with TNF and chemotherapy we observed a rise in VEGF-A, SCF, VEGFR-2, MMP-9, Tie-2 and CRP, a correlation between CRP and IL-8, and a decreased in sVEGFR-1 levels. In conclusion, among all factors measured, only VEGF-A and MMP-9 consistently correlated to each other, elevated CRP levels were associated with tumor burden, whereas sVEGF-R1 increased after tumor removal in colorectal cancer. Treatment with chemotherapy and TNF induced changes consistent with an angiogenic switch. These results warrant a prospective study to compare the effect of surgical tumor removal vs. chemotherapy on some of these markers and to evaluate their prognostic/predictive value.
authors.affiliation: Centre Pluridisciplianire d'Oncologie (CePO), Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
authors.forename: Khalil
authors.initials: K
authors.lastname: Zaman
authors.forename: Robert
authors.initials: R
authors.lastname: Driscoll
authors.forename: Diane
authors.initials: D
authors.lastname: Hahn
authors.forename: Patricia
authors.initials: P
authors.lastname: Werffeli
authors.forename: Simon L
authors.initials: SL
authors.lastname: Goodman
authors.forename: Jean
authors.initials: J
authors.lastname: Bauer
authors.forename: Serge
authors.initials: S
authors.lastname: Leyvraz
authors.forename: Ferdy
authors.initials: F
authors.lastname: Lejeune
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Curzio
authors.initials: C
authors.lastname: Rüegg
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000601:surgery; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008545:Melanoma / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D009361:Neoplasm Invasiveness; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D009389:Neovascularization, Pathologic; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9