Down-regulation of Platelet-Derived Growth Factor-D Inhibits Cell Growth and Angiogenesis through Inactivation of Notch-1 and Nuclear Factor-κB Signaling

Wang, Zhiwei; Kong, Dejuan; Banerjee, Sanjeev; Li, Yiwei; Adsay, Volkan; Abbruzzese, James L.; Sarkar, Fazlul H.

doi:10.1158/0008-5472.can-07-2803

Cited by 113 publications

(128 citation statements)

References 32 publications

(62 reference statements)

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“…Greater benefit for overall survival was observed for patients treated with erlotinib plus gemcitabine who had wild-type K-Ras, however, this finding was not significant (p00.34). All of the pancreatic cancer cell lines used in this study carry mutated K-Ras, except BxPc-3 [33] (www.sanger.ac.uk/genetics/CGP/cosmic/), which is also the cell line that is most sensitive to lapatinib. Three of the four K-Ras mutated cell lines are resistant to erlotinib at concentrations up to 10 μM but display sensitivity to lapatinib with IC 50 s ranging from 2.3-4.1 μM.…”

Section: Discussionmentioning

confidence: 99%

EGFR and HER2 inhibition in pancreatic cancer

et al. 2012

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Summary The aim of this study was to investigate the effect of lapatinib, a selective inhibitor of EGFR/HER2 tyrosine kinases, on pancreatic cancer cell lines both alone and in combination with chemotherapy. Two cell lines, BxPc-3 and HPAC, displayed the greatest sensitivity to lapatinib (IC 50 < 2 μM). Lapatinib also demonstrated some activity in three KRas mutated pancreatic cancer cell lines which displayed resistance to erlotinib. Drug effect/combination index (CI) isobologram analysis was used to study the interactions of lapatinib with gemcitabine, cisplatin and 5'deoxy-5'fluorouridine. Concentration-dependent anti-proliferative effects of lapatinib in combination with chemotherapy were observed. To evaluate the potential effect of lapatinib in pancreatic cancer tumours, and to identify a subset of patient most likely to benefit from lapatinib, expression of EGFR and HER2 were investigated in 72 pancreatic cancer tumour specimens by immunohistochemistry. HER2 membrane expression was observed in only 1 % of cases, whereas 44 % of pancreatic tumours expressed EGFR. Based on our in vitro results, lapatinib may provide clinical benefit in EGFR positive pancreatic ductal adenocarcinoma.

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Section: Discussionmentioning

confidence: 99%

EGFR and HER2 inhibition in pancreatic cancer

et al. 2012

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“…Notch signaling enhances primary melanoma metastasis through effects on b-catenin signaling. 17 In addition, Notch signaling also regulates NFjB-DNA binding, 18 which affects genes that are critical for metastasis. Some recent studies have demonstrated the transcriptional activation of MMP9 and uPA by Notch1 in human prostate cancer 19 and the participation of Notch1 signaling in pancreatic cancer 20 and osteosarcoma.…”

mentioning

confidence: 99%

Notch1‐Snail1‐E‐cadherin pathway in metastatic hepatocellular carcinoma

Wang

Zhang

Lui

et al. 2011

Intl Journal of Cancer

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Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the reestablishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis.Hepatocellular carcinoma (HCC) is the fifth most common cancer globally and is ranked second amongst all cancer deaths in Hong Kong. HCC is correlated with an increased likelihood of vascular invasion, metastasis and recurrence (even after surgical resection), leading to poor prognosis. 1 Metastasis, both intrahepatic and extrahepatic, is of particular concern and occurs in more than half of HCC cases. 2 The incidence of high grade HCC that metastasize to distant sites is high. 2 However, the detailed mechanisms of metastasis are yet to be revealed.The process that converts adherent epithelial cells into migratory cells to invade the extracellular matrix is called the epithelial-mesenchymal transition (EMT). This process plays fundamental roles in tissue and organ formation during embryonic development and in wound healing and tissue repair during adult life. 3,4 However, the abnormal activation of EMT programs can be disadvantageous to cancer patients. 3 EMT can allow carcinoma cells to acquire mesenchymal cell gene expression profiles and properties, 5 leading to the transformation of the cells from being coherent and displaying apicobasal polarity to become nonpolarized cells that can move through the extracellular media. This transformation enables the spread of tumor cells to distant sites. 6,7 Although EMT is considered to be the first step in the metastatic progression of migratory cancer cells, EMT has not been confirmed to exist in vivo. 3...

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“…PDGF has also been identified as a significant contributor to angiogenesis and cardiac remodeling following MI [56][57][58] . Notably, both VEGF and PDGF have demonstrated some adverse effects, particularly when given in high intravenous doses.…”

Section: Cytokines Role "Vegf and Pdgf"mentioning

confidence: 99%