TY - JOUR
T1 - Suppression of angiogenesis and therapy of human colon cancer liver metastasis by systemic administration of interferon-α1
AU - Ozawa, S.
AU - Shinohara, H.
AU - Kanayama, H. O.
AU - Bruns, C. J.
AU - Bucana, C. D.
AU - Ellis, L. M.
AU - Davis, D. W.
AU - Fidler, I. J.
N1 - Funding Information:
Abbreviations: bFGF, basic fibroblast growth factor; FBS, fetal bovine saerum; IFN-α, interferon-alpha; IHC, immunohistochemistry; IL, interleukin; ISH, in situ hybridization; EMEM, Eagle's minimum essential medium; MMP, matrix metalloprotease; MVD, microvessel density; VEGF/VPF, vascular endothelial growth factor/vascular permeability factor; MMP, matrix metalloprotease; PCNA, proliferative cell nuclear antigen; TUNEL, TdT-mediated dUTP-biotin nick-end labeling Address all correspondence to: Isaiah J. Fidler, DVM, PhD, Department of Cancer Biology, Box 173, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. E-mail: [email protected] 1This work was supported in part by Cancer Center Support Core grant CA16672 and grant R35-CA42107 from the National Cancer Institute, National Institutes of Health, and by the SPORE in Ovarian Cancer grant P50-CA83639 from the National Institutes of Health. Received 17 October 2000; Accepted 1 December 2000.
PY - 2001
Y1 - 2001
N2 - The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-α) can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-α-sensitive) or KM12L4 IFNR (IFN-α- resistant) cells were injected into the spleen of nude mice. Seven days later, the mice were treated with subcutaneous (s.c.) injections of IFN-α (70,000 units/week) at different dosing schedules (1, 2, or 7 times/week). Significant inhibition of tumor growth, vascularization and expression of basic fibroblast growth factor (bFGF) or matrix metalloproteinase-9 (MMP-9) mRNA and protein occurred in mice given daily injections of IFN-α. Kinetic analysis of therapy showed that daily s.c. administrations of 10,000 units of IFN-α induced apoptosis in liver metastasis - associated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activity of IFN-α2a depends on frequent administration of the optimal biologic dose.
AB - The purpose of this study was to determine whether systemic administration of interferon-alpha (IFN-α) can inhibit liver metastasis produced in nude mice by human colon cancer cells. KM12L4 (IFN-α-sensitive) or KM12L4 IFNR (IFN-α- resistant) cells were injected into the spleen of nude mice. Seven days later, the mice were treated with subcutaneous (s.c.) injections of IFN-α (70,000 units/week) at different dosing schedules (1, 2, or 7 times/week). Significant inhibition of tumor growth, vascularization and expression of basic fibroblast growth factor (bFGF) or matrix metalloproteinase-9 (MMP-9) mRNA and protein occurred in mice given daily injections of IFN-α. Kinetic analysis of therapy showed that daily s.c. administrations of 10,000 units of IFN-α induced apoptosis in liver metastasis - associated endothelial cells, followed by inhibition of tumor cell division and apoptosis of tumor cells. These data suggest that the antiangiogenic activity of IFN-α2a depends on frequent administration of the optimal biologic dose.
KW - Angiogenesis
KW - Apoptosis
KW - Interferon
UR - https://www.scopus.com/pages/publications/0035043493
UR - https://www.scopus.com/pages/publications/0035043493#tab=citedBy
U2 - 10.1038/sj.neo.7900128
DO - 10.1038/sj.neo.7900128
M3 - Article
C2 - 11420751
AN - SCOPUS:0035043493
SN - 1522-8002
VL - 3
SP - 154
EP - 164
JO - Neoplasia
JF - Neoplasia
IS - 2
ER -