title: Serum IGF-I, IGFBP-3, and matrix metalloproteinase-7 levels and acquired chemo-resistance in advanced colorectal cancer.
abstract: Insulin-like growth factor-I (IGF-I) is thought to have antiapoptotic and mitogenic properties in colorectal cancer, whereas IGF-binding protein-3 (IGFBP-3) seems to exert a pro-apoptotic effect. Additionally, matrix metalloproteinase-7 (MMP-7), an enzyme with in vitro ability to degrade IGFBP-3, has been shown to be a prognostic factor in advanced colorectal cancer (ACRC). We studied whether chemotherapy treatment for ACRC modulates IGF-I, IGFBP-3, and MMP-7 serum levels. In 41 patients undergoing first-line therapy for ACRC, serum levels of IGF-I, IGFBP-3, and MMP-7 were measured with immunoassays at baseline and every 3 months until progressive disease, or a maximum of five determinations, during a chemotherapy regimen of either FOLFOX or FOLFIRI therapies. Associations were assessed for paired samples, using t-test or Wilcoxon ranks test depending on normality of the variable, verified with Shapiro-Wilk test. An average of four extractions (range 3-5) were done, for a total of 157 determinations. Mean pretreatment values of IGF-I, IGFBP-3, and MMP-7 were 83 (95% CI, 73-92) ng/ml, 2372 (95% CI, 2121-2623) ng/ml, and 10.6 (95% CI, 7.21-13.98) ng/ml respectively. No significant changes in IGF-I were found, but a significant increase in IGFBP-3 serum concentrations was observed during or after chemotherapy treatment without progressive disease, compared with basal levels (P<0.001). A significant decrease in IGFBP-3 to 1983 ng/ml (95% CI, 1675-2292) and a significant increase in MMP-7 levels to 14.6 (7.6-21.7) ng/ml were observed at progression of disease compared with baseline and treatment levels (P<0.001). This study shows that IGFBP-3 and MMP-7 serum levels change during chemotherapy treatment. The increased MMP-7 levels at disease progression support the hypothesis that this protease could play a role in acquired resistance by degrading IGFBP-3.
authors.affiliation: Department of Medical Oncology, Hospital Clínic Barcelona, Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Gallego
authors.forename: Jordi
authors.initials: J
authors.lastname: Codony-Servat
authors.forename: Xabier
authors.initials: X
authors.lastname: García-Albéniz
authors.forename: Enric
authors.initials: E
authors.lastname: Carcereny
authors.forename: Raquel
authors.initials: R
authors.lastname: Longarón
authors.forename: Angeles
authors.initials: A
authors.lastname: Oliveras
authors.forename: Mónica
authors.initials: M
authors.lastname: Tosca
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Augé
authors.forename: Pedro
authors.initials: P
authors.lastname: Gascón
authors.forename: Joan
authors.initials: J
authors.lastname: Maurel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000097:blood*; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D009944:Organoplatinum Compounds; D007334:Insulin-Like Growth Factor I; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin