Generation of multiple angiogenesis inhibitors by human pancreatic cancer.
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Generation of multiple angiogenesis inhibitors by human pancreatic cancer. / Kisker, O; Onizuka, S; Banyard, J; Komiyama, T; Becker, C M; Achilles, Eike-Gert; Barnes, C M; O'Reilly, M S; Folkman, J; Pirie-Shepherd, S R.
in: CANCER RES, Jahrgang 61, Nr. 19, 19, 2001, S. 7298-7304.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Generation of multiple angiogenesis inhibitors by human pancreatic cancer.
AU - Kisker, O
AU - Onizuka, S
AU - Banyard, J
AU - Komiyama, T
AU - Becker, C M
AU - Achilles, Eike-Gert
AU - Barnes, C M
AU - O'Reilly, M S
AU - Folkman, J
AU - Pirie-Shepherd, S R
PY - 2001
Y1 - 2001
N2 - A primary inoculum of human pancreatic cancer cells (BxPC-3) has the ability to inhibit the growth of a secondary tumor in an in vivo animal model. Such ability suggests that the primary tumor is producing inhibitors that act at the site of the secondary tumor. Accordingly we attempted to discover which inhibitors are produced by pancreatic cancer cells. We determined that pancreatic cancer cells process angiostatin isoforms from plasminogen. Additionally, we isolated and characterized an uncleaved "latent" antiangiogenic antithrombin (aaAT) molecule processed from systemically available AT by pancreatic cancer cells as well as a cleaved form of aaAT processed from systemically available AT by pancreatic cancer cells. Human AT, cleaved with human neutrophil elastase, inhibits angiogenesis in the chorioallantoic membrane assay. This human aaAT molecule is able to inhibit the growth of pancreatic tumors in immune-compromised mice. Our work represents the first demonstration of multiple angiogenesis inhibitors from a single tumor and suggests that antiangiogenic therapies may provide an avenue for future treatment of pancreatic cancer.
AB - A primary inoculum of human pancreatic cancer cells (BxPC-3) has the ability to inhibit the growth of a secondary tumor in an in vivo animal model. Such ability suggests that the primary tumor is producing inhibitors that act at the site of the secondary tumor. Accordingly we attempted to discover which inhibitors are produced by pancreatic cancer cells. We determined that pancreatic cancer cells process angiostatin isoforms from plasminogen. Additionally, we isolated and characterized an uncleaved "latent" antiangiogenic antithrombin (aaAT) molecule processed from systemically available AT by pancreatic cancer cells as well as a cleaved form of aaAT processed from systemically available AT by pancreatic cancer cells. Human AT, cleaved with human neutrophil elastase, inhibits angiogenesis in the chorioallantoic membrane assay. This human aaAT molecule is able to inhibit the growth of pancreatic tumors in immune-compromised mice. Our work represents the first demonstration of multiple angiogenesis inhibitors from a single tumor and suggests that antiangiogenic therapies may provide an avenue for future treatment of pancreatic cancer.
M3 - SCORING: Zeitschriftenaufsatz
VL - 61
SP - 7298
EP - 7304
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 19
M1 - 19
ER -
