Co-overexpression of Met and Hepatocyte Growth Factor Promotes Systemic Metastasis in NCI-H460 Non-Small Cell Lung Carcinoma Cells

Navab, Roya; Liu, Jiang; Seiden‐Long, Isolde; Shih, Warren; Li, Ming; Bandarchi, Bizhan; Chen, Yan; Lau, Davina; Zu, Yen-Fen; Cescon, DW; Zhu, Chang-Qi; Organ, Shawna; Ibrahimov, Emin; Ohanessian, Dina; Tsao, Ming‐Sound

doi:10.1593/neo.09622

Cited by 66 publications

(51 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…3B). H460 tumors are highly vascularized (Mukhopadhyay et al, 2002;Navab et al, 2009) but have heterogeneous regions of hypoxia (Lam et al, 2009), in agreement with our findings. AQ4N Is More Toxic to scid Mice Than Nude Mice.…”

Section: Resultssupporting

confidence: 92%

Impact of Tumor Blood Flow Modulation on Tumor Sensitivity to the Bioreductive Drug Banoxantrone

Manley

Waxman

2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

We investigated the hypoxia-dependent cytotoxicity of AQ4N (banoxantrone) using a panel of 13 cancer cell lines and studied its relationship to the expression of the quinone reductase DTdiaphorase (NQO1), which is widely found in cancer cells. We also investigated pharmacologic treatments that increase tumor hypoxia in vivo and their impact on AQ4N chemosensitivity in a solid tumor xenograft model. AQ4N showed $8-fold higher cytotoxicity under hypoxia than normoxia in cultures of 9L rat gliosarcoma and H460 human non-small-cell lung carcinoma cells but not for 11 other human cancer cell lines. DT-diaphorase protein levels and AQ4N chemosensitivity were poorly correlated across the cancer cell line panel, and AQ4N chemosensitivity was not affected by DT-diaphorase inhibitors. The vasodilator hydralazine decreased tumor perfusion and increased tumor hypoxia in 9L tumor xenografts, and to a lesser extent in H460 tumor xenografts. However, hydralazine did not increase AQ4N-dependent antitumor activity. Combination of AQ4N with the angiogenesis inhibitor axitinib, which increases 9L tumor hypoxia, transiently increased antitumor activity but with an increase in host toxicity. These findings indicate that the capacity to bioactivate AQ4N is not dependent on DTdiaphorase and is not widespread in cultured cancer cell lines. Moreover, the activation of AQ4N cytotoxicity in vivo requires tumor hypoxia that is more extensive or prolonged than can readily be achieved by vasodilation or by antiangiogenic drug treatment.

show abstract

Section: Resultssupporting

confidence: 92%

Impact of Tumor Blood Flow Modulation on Tumor Sensitivity to the Bioreductive Drug Banoxantrone

Manley

Waxman

2012

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…IHC protocols were described previously (32). The staining intensity of CCD68 antibody (Sigma; SAB1103198,1:3000) was scored by a certified pathologist on a scale from 0–3 (0=absent; 1=low; 2=medium; 3=high).…”

Section: Methodsmentioning

confidence: 99%

Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role in pancreatic ductal adenocarcinoma

et al. 2014

View full text Add to dashboard Cite

Using integrative genomics and functional screening we identified coiled-coil domain containing 68 (CCDC68) as a novel putative tumor suppressor (TSG) in pancreatic ductal adenocarcinoma (PDAC). CCDC68 allelic losses were documented in 48% of primary PDAC patient tumors, 50% of PDAC cell lines, and 30% of primary patient derived xenografts. We also discovered a SNP variant (SNP rs1344011) that leads to exon skipping and generation of an unstable protein isoform CCDC68Δ69–114 in 31% of PDAC patients. Overexpression of full length CCDC68 (CCDC68wt) in PANC-1 and Hs.766T PDAC cell lines lacking CDCC68 expression decreased proliferation and tumorigenicity in scid mice. In contrast, downregulation of endogenous CCDC68 in MIAPaca-2 cells increased tumor growth rate. These effects were not observed with the deletion-containing isoform, CCDC68Δ69–114. In conclusion, our results suggest that CCDC68 is a novel candidate TSG in PDAC.

show abstract

“…HGF/cMET signaling prevents apoptosis through the phosphorylation of phosphatidylinositol-3-kinase and subsequent Akt activation (12,13). A number of reports have identified that the overexpression of HGF and cMET are associated with cancer invasion, metastasis and poor prognosis in various cancers (14)(15)(16)(17)(18). HGF, known as a scatter factor, is a mesenchymal cytokine with pleiotropic effects, including mitogenic, motogenic and morphogenic properties, and plays an important role in angiogenesis and tumor growth via promoting angiogenic mediators, including vascular endothelial growth factor (VEGF) (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of HGF/cMET expression prevents distant recurrence of rectal cancer after preoperative chemoradiotherapy

Saigusa

Toiyama²,

Yokoe³

et al. 2011

Int J Oncol

View full text Add to dashboard Cite

Abstract. Hepatocyte growth factor (HGF) and its receptor cMET play an important role in tumor proliferation, invasion and metastasis. In this study, we investigated the association of HGF/cMET signaling with distant recurrence in rectal cancer after preoperative chemoradiotherapy and whether inhibition of the HGF/cMET signaling pathway could suppress the re-growth of cancer cells after irradiation. We obtained total RNA from residual cancer cells and stromal tissue separately using microdissection from a total of 53 rectal cancer specimens from patients who underwent preoperative CRT, performed transcriptional analyses, and analyzed the association of HGF and cMET expression levels with clinical outcomes. We performed in vitro experiments to examine HGF and cMET expression and the re-growth of cancer cells after irradiation and treatment with a tyrosine kinase inhibitor specific for cMET (SU11274). We found significant correlations between cancer cell HGF and cMET gene expression, and stromal cell HGF and cancer cell cMET expression. Elevated cancer cell cMET and stromal HGF expression were significantly associated with a worse prognosis. In vitro experiments showed that the up-regulation of HGF expression and the re-growth of irradiated cancer cells were effectively suppressed by inhibiting cMET. Our results suggest that inhibition of radiation-induced HGF up-regulation and blockade of autocrine/paracrine HGF/ cMET signaling are potential new strategies for controlling distant recurrence in rectal cancer patients after preoperative CRT.

show abstract

Co-overexpression of Met and Hepatocyte Growth Factor Promotes Systemic Metastasis in NCI-H460 Non-Small Cell Lung Carcinoma Cells

Cited by 66 publications

References 27 publications

Impact of Tumor Blood Flow Modulation on Tumor Sensitivity to the Bioreductive Drug Banoxantrone

Impact of Tumor Blood Flow Modulation on Tumor Sensitivity to the Bioreductive Drug Banoxantrone

Coiled-coil domain containing 68 (CCDC68) demonstrates a tumor-suppressive role in pancreatic ductal adenocarcinoma

Inhibition of HGF/cMET expression prevents distant recurrence of rectal cancer after preoperative chemoradiotherapy

Contact Info

Product

Resources

About