Cyclooxygenase-2 selective inhibition with NS-398 suppresses proliferation and invasiveness and delays liver metastasis in colorectal cancer

Yao, Min; Lam, Eugene; Kelly, Colleen R.; Zhou, Wei; Wolfe, M. Michael

doi:10.1038/sj.bjc.6601489

Cited by 101 publications

(80 citation statements)

References 56 publications

(62 reference statements)

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“…Another relevant outcome of this study was the documentation of the expression of COX-2, c-KIT and HER-2/neu in uterine carcinosarcomas, because we know that these same gene products are molecular targets for innovative treatments, such as COX-2 inhibitors, STI571 and trastuzumab, which had been already proven beneficial in colorectal cancer, GIST and breast carcinoma, respectively [16,41,42].…”

Section: Discussionmentioning

confidence: 99%

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

Raspollini

Susini

Amunni

et al. 2005

Gynecologic Oncology

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Objectives. Uterine carcinosarcomas are uncommon, highly aggressive neoplasms that frequently recur after surgical treatment and adjuvant chemo-radiotherapy. Patients with recurrent disease respond poorly to salvage chemotherapy and irradiation. New therapeutic options are required for patients with metastatic disease. Clinical evidences showing the effect of a tyrosine kinase inhibitor, STI571, in c-KIT-positive gastrointestinal tumors, the role of COX-inhibitors chemotherapy-associated in colorectal cancer patients and the successful therapeutic possibility of anti-HER2 therapy in metastatic breast carcinoma, have encouraged us to study the expression of c-KIT, COX-2 and HER-2/neu in uterine carcinosarcomas.Methods. We analyzed the expression of COX-2, c-KIT and HER-2/neu in 24 uterine carcinosarcomas and their correlation with clinical outcome. Disease-free interval and actuarial survival rates were the end points of the study.Results. High staining intensity for COX-2 was observed in 8 cases (33.3%). C-KIT was expressed in 4 cases (16.7%) and HER-2/neu in 7 cases (29.2%). Patients with COX-2-positive tumors had a significantly poorer disease-free interval and survival ( P = 0.01 and P = 0.05, respectively). All patients with c-KIT-positive tumors had early stage disease. In spite of this, their survival was not significantly better than that of c-KIT-negative cases. HER-2/neu expression did not show any correlation with clinical outcome.Conclusion. c-KIT, COX-2, and HER-2/neu were expressed in different proportions of uterine carcinosarcomas. COX-2 expression was a strong indicator of unfavorable prognosis. These results warrant further study to evaluate the possible role of a new molecularly targeted cancer therapy with COX-2 inhibitors in patients with uterine carcinosarcomas. The role of c-KIT expression and consequently the hypothetical use of STI571 should be tested in a larger series.

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Section: Discussionmentioning

confidence: 99%

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

Raspollini

Susini

Amunni

et al. 2005

Gynecologic Oncology

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“…These effects of tumor COX-2-dependent factors on tumor-activated LSECs are consistent with reported antimetastatic effects of COX-2 inhibitors in the liver. 38 Finally, C26 cell-derived factors impaired LSL-stimulating effects of LSECs leading to anti-tumor cytotoxicity inhibition and IFN-gamma/IL-10 secretion ratio decrease. Nonetheless, ManR deficiency in ManR À/À mice and blockade of ManR on tumor-stimulated LSECs-either directly with specific neutralizing antibodies or indirectly by inhibition of ManR-stimulating factor production through IL-1 and COX-2 inhibitors-restored antitumor cytotoxicity of LSLs interacting with tumor-activated LSECs.…”

Section: Discussionmentioning

confidence: 99%

Colon Carcinoma Cell Interaction With Liver Sinusoidal Endothelium Inhibits Organ-Specific Antitumor Immunity Through Interleukin-1-Induced Mannose Receptor in Mice

et al. 2010

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Mannose receptor (ManR)-mediated liver sinusoidal endothelial cell (LSEC) endocytosis plays a role in antigen presentation and innate immunity, but its role in hepatic metastasis is unknown. We studied ManR-mediated endocytosis during C26 colorectal cancer cell interaction with LSECs and its implications in metastasis. Uptake of labeled ManR ligands (mannan and ovalbumin) and immunohistochemistry were used to study ManR endocytosis and expression. Several interleukin (IL)-1 inhibitors and the cyclooxygenase-2 (COX-2) inhibitor celecoxib were used to analyze the role of IL-1 and COX-2 in ManR regulation. Anti-mouse ManR antibodies and ManR knockout (ManR 2/2 ) mice were used to identify ManR-dependent mechanisms during antitumor immune response of liver sinusoidal lymphocytes (LSLs) interacting with tumor-activated LSECs. ManR expression and endocytosis increased in tumor-activated LSECs through a two-step mechanism:(1) Release of COX-2-dependent IL-1-stimulating factors by lymphocyte function-associated antigen-1-expressing C26 cells in response to intercellular adhesion molecule-1 (ICAM-1), which was expressed and secreted by tumor-activated LSECs; and (2) widespread up-regulation of ManR in LSECs through tumor-induced IL-1. In addition, LSLs that had interacted with tumoractivated LSECs in vivo decreased their antitumor cytotoxicity and interferon (IFN)-gamma secretion while they increased IL-10 release ex vivo. IFN-gamma/IL-10 ratio also decreased in the hepatic blood from tumor-injected mice. Immunosuppressant effects of tumor-activated LSECs on LSLs were abrogated in both LSECs from ManR 2/2 mice and tumor-activated LSECs given antimouse ManR antibodies. Conclusion: ICAM-1-induced tumor COX-2 decreased antitumor activity during hepatic metastasis through IL-1-induced ManR. ManR constituted a common mediator for prometastatic effects of IL-1, COX-2, and ICAM-1. A rise in hepatic IFN-gamma/IL-10 ratio and antitumor cytotoxicity by way of ManR blockade is consistent with the antimetastatic effects of IL-1, COX-2, and ICAM-1 inhibitors. These data support ManR and ManR-stimulating factors as targets for hepatic colorectal metastasis therapy. (HEPATOLOGY 2010;51:2172-2182 Abbreviations: ASMA, alpha-smooth muscle actin; CM, cell-conditioned medium; COX-2, cyclooxygenase-2; CSPG, chondroitin sulfate proteoglycan; ELISA, enzyme-linked immunosorbent assay; FITC-OVA, fluorescein isothiocyanate-labeled ovalbumin; FSA, formaldehyde treated serum albumin; ICAM-1, intercellular adhesion molecule-1; ICE, IL-1-converting enzyme; IgG2a, immunoglobulin G2a; IL, interleukin; IL-1RI, IL-1 receptor type I; IL-1Ra, IL-1 receptor antagonist; LFA-1, lymphocyte function-associated antigen 1; LSEC, liver sinusoidal endothelial cell; LSL, liver sinusoidal lymphocyte; ManR, mannose receptor; ManR À/À , ManR knockout; SD, standard deviation; sICAM-1, soluble ICAM-1.From the

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“…This can reduce tumor cell proliferation and invasion. It has also been shown that COX-2 inhibitor significantly reduced tumor-induced MMP-2 and MMP-9 expression in cancer models (21,46). To elucidate the possible link between COX-2/VEGFR and the proteolytic enzymes, cells were treated with SC-236 or CBO-P11 to examine the effects on MMP-2 and MMP-9 as well as uPA and uPAR on gastric cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…MMPs are involved in ECM degradation (17) and the activity is associated with invasiveness and metastasis in tumor cells (18). MMP-2 and MMP-9 are the two major enzymes that can selectively degrade type IV collagen and facilitate tumor invasion and metastasis in various experimental models, including gastric, colon, and breast cancers (19)(20)(21). Administration of nicotine increased the severity of choroidal neovascularization and also reversed the VEGF-induced suppression of MMP-2 activity in mice (22), showing that MMP could play a role in the angiogenesis induced by nicotine.…”

Section: Introductionmentioning

confidence: 99%

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

Shin¹,

Wu²,

Chu³

et al. 2005

Molecular Cancer Research

107

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Blockade of angiogenesis is a promising strategy to suppress tumor growth, invasion, and metastasis. Vascular endothelial growth factor (VEGF), which binds to tyrosine kinase receptors [VEGF receptors (VEGFR) 1 and 2], is the mediator of angiogenesis and mitogen for endothelial cells. Cyclooxygenase-2 (COX-2) plays an important role in the promoting action of nicotine on gastric cancer growth. However, the action of nicotine and the relationship between COX-2 and VEGF/VEGFR system in tumorigenesis remain undefined. In this study, the effects of nicotine in tumor angiogenesis, invasiveness, and metastasis were studied with sponge implantation and Matrigel membrane models. Nicotine (200 Mg/mL) stimulated gastric cancer cell proliferation, which was blocked by SC-236 (a highly selective COX-2 inhibitor) and CBO-P11 (a VEGFR inhibitor). This was associated with decreased VEGF levels as well as VEGFR-2 but not VEGFR-1 expression. Topical injection of nicotine enhanced tumor-associated vascularization, with a concomitant increase in VEGF levels in sponge implants. Again, application of SC-236 (2 mg/kg) and CBO-P11 (0.4 mg/kg) partially attenuated vascularization by f30%. Furthermore, nicotine enhanced tumor cell invasion through the Matrigel membrane by 4-fold and promoted migration of human umbilical vein endothelial cells in a cocultured system with gastric cancer cells. The activity of matrix metalloproteinases 2 and 9 and protein expressions of plasminogen activators (urokinase-type plasminogen activator and its receptor), which are the indicators of invasion and migration processes, were increased by nicotine but blocked by COX-2 and VEGFR inhibitors. Taken together, our results reveal that the promoting action of nicotine on angiogenesis, tumor invasion, and metastasis is COX-2/VEGF/VEGFR dependent. (Mol Cancer Res 2005;3(11):607 -15)

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Cyclooxygenase-2 selective inhibition with NS-398 suppresses proliferation and invasiveness and delays liver metastasis in colorectal cancer

Cited by 101 publications

References 56 publications

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

Colon Carcinoma Cell Interaction With Liver Sinusoidal Endothelium Inhibits Organ-Specific Antitumor Immunity Through Interleukin-1-Induced Mannose Receptor in Mice

Nicotine Induces Cyclooxygenase-2 and Vascular Endothelial Growth Factor Receptor-2 in Association with Tumor-Associated Invasion and Angiogenesis in Gastric Cancer

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