scholarly journals Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer

Oncotarget ◽  
2014 ◽  
Vol 6 (7) ◽  
pp. 5164-5181 ◽  
Author(s):  
Parthasarathy Seshacharyulu ◽  
Moorthy P. Ponnusamy ◽  
Satyanarayana Rachagani ◽  
Imayavaramban Lakshmanan ◽  
Dhanya Haridas ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Egf Receptor ◽  
Human Pancreatic Cancer ◽  
Tumor Growth And Metastasis

scholarly journals Expression of core 3 synthase in human pancreatic cancer cells suppresses tumor growth and metastasis

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Prakash Radhakrishnan ◽  
Paul M. Grandgenett ◽  
Ashley M. Mohr ◽  
Stephanie K. Bunt ◽  
Fang Yu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Tumor Growth And Metastasis

scholarly journals Leukemia-related protein 16 (LRP16) promotes tumor growth and metastasis in pancreatic cancer

2018 ◽  
Vol Volume 11 ◽  
pp. 1215-1222 ◽  
Author(s):  
Zheng Mo ◽  
Minggen Hu ◽  
Fei Yu ◽  
Lijuan Shao ◽  
Kexing Fan ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Related Protein ◽  
Tumor Growth And Metastasis

Expression of Alternatively-Spliced Human Tissue Factor, but Not Full-Length Tissue Factor, Enhances Tumor Growth and Tumor-Associated Vasculature.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1746-1746
Author(s):  
Gerald A. Soff ◽  
Jennifer Hobbs ◽  
Emily Hyman ◽  
Deborah L. Cundiff
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Tissue Factor ◽  
Human Tissue ◽  
Primary Tumor ◽  
Conditioned Media ◽  
Full Length ◽  
Human Pancreatic Cancer ◽  
Primary Tumor Growth ◽  
Alternatively Spliced

Abstract It is well-established that cancer is associated with activation of the blood coagulation system, with associated thrombosis as a major cause of morbidity and mortality. Increased expression of Tissue Factor (TF) by cancer cells correlates with a more aggressive grade and clinical course. It is widely presumed that activation of coagulation facilitates cancer growth, and in mouse models, anticoagulation can reduce development of lung metastases. Yet primary tumors are not reduced in a fibrinogen knock-out mouse host, and most importantly, anticoagulation has not been shown to reduce tumor growth in cancer patients. We therefore studied the effect of expression of full-length Tissue Factor (FLTF) and alternatively-spliced human Tissue Factor (asHTF) in a mouse model of human pancreatic cancer. Due to the loss of exon 5, asHTF has a truncated extracellular domain with incomplete procoagulant activity. And due to a frame shift, exon 6 does not code for the transmembrane domain and cytoplasmic tail of FLTF, but codes for a novel peptide sequence. asHTF is soluble and of unknown function. We show that 5 of 6 human pancreatic cancer cell lines tested expressed both FLTF as well as asHTF. The MiaPaca-2 line did not express detectable mRNA or protein of either TF isoform. We generated mammalian expression vectors for both FLTF and asHTF, and established Miapaca-2 clones, stably expressing FLTF, asHTF, or control clones with an empty vector. As anticipated, conditioned media from all FLTF clones shortened the whole blood clotting times by approximately 75%. Conditioned media from control cells and asHTF expressing cells had no effect on clotting times. To evaluate the effect of the TF isoforms on primary tumor growth, 5 X 106 cells from three independent clones of stably transfected clones of FLTF, asHTF, or control clones were injected into the flanks of nude mice (4 mice per clone). At 31 days, the mice were sacrificed and tumor mass measured. Tumors grew in 10 of 12 control mice, but were small (mean tumors 90 mg, SEM 21 mg). Interestingly, FLTF was associated with reduced primary tumor growth; only 4 of 12 developed measurable tumors (mean tumors 10 mg, SEM 4 mg, p = 0.002). In contrast, asHTF expression was associated with enhanced tumor growth; 12 of 12 animals developed tumors (mean tumors 390 mg, SEM 102 mg, p=0.018). In animals with asHTF expressing tumors, circulating asHTF protein was observed in the plasma. The asHTF tumors had increased vascular density compared with controls, suggesting a role of asHTF promoting angiogenesis. In contrast to the prevailing paradigm, our data suggest that FLTF, with procoagulant activity, not only fails to promote primary tumor growth, but may actually inhibit tumor growth. In contrast, asHTF, may be the more important TF isoform in the enhancement of tumor growth.

Inhibition of cMET in an experimental model of pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 185-185
Author(s):  
Sven A. Lang ◽  
Franziska Brandes ◽  
Edward K. Geissler
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Oncogenic Signaling

185 Background: In human pancreatic cancer, expression of cMET is associated with poor survival. So far, activation/expression of cMET by hepatocyte growth factor (HGF) has been shown to induce proliferation and motility in cancer cells. Therefore, we hypothesized that inhibition of cMET in human pancreatic cancer cell lines impairs oncogenic signaling and tumor growth. Methods: Pancreatic cancer cell lines (HPAF-II, MiaPaCa2, L3.6pl, BxPC3, Panc02) and the cMET inhibitor INC280 (Novartis Oncology, Basel) were used. MiaPaCa2 and L3.6pl pancreatic cancer cells were grown with gemcitabine up to 500 and 250 nM, respectively (then called MiaPaCa2(G500) and L3.6pl(G250)). MTT and Boyden Chamber assays were used to determine effects of INC280 on growth and motility of cells in vitro. Expression of growth factor receptors, activation of signaling intermediates and expression of transcription factors were assessed by Western blotting. Finally, in vitro results were validated in an orthotopic tumor model using L3.6pl pancreatic cancer cell line. Results: All pancreatic cancer cell lines showed expression of cMET. In vitro treatment of cancer cells with INC280 led to a minor, dose-dependent inhibition of growth even when cells were supplemented with HGF. In contrast, migration assays showed a significant reduction of cancer cell motility upon INC280 when cells were stimulated with HGF (P<0.05). Regarding oncogenic signaling, INC280 led to inhibition of HGF-induced phosphorylation of AKT, ERK and FAK. In addition, c-Myc expression was diminished in cancer cells. Interestingly, gemcitabine resistant cell line MiaPaCa2(G500) showed higher cMET expression levels compared to the normal MiaPaCa2. Stimulation of MiaPaCa2(G500) with HGF led to strong induction of oncogenic signaling and tumor cell motility, an effect that was significantly diminished by INC280. Moreover, results from in vivo experiments show that therapy with INC280 (10 mg/kg/d) significantly reduces tumor growth as determined by final tumor weight (P<0.05). Conclusions: In pancreatic cancer cell lines, targeting cMET with INC280 abrogates oncogenic signaling in vitro and impairs tumor growth in vivo. Therefore, the concept of cMET inhibition warrants further preclinical evaluation.

scholarly journals miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer

2014 ◽  
Vol 10 (5) ◽  
pp. 2613-2620 ◽  
Author(s):  
JIAN LI ◽  
FUJIAO KONG ◽  
KEMIN WU ◽  
KUN SONG ◽  
JIANFENG HE ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Tumor Growth And Metastasis

scholarly journals UVC Radiation Induces Downregulation of EGF Receptor via Phosphorylation at Serine 1046/1047 in Human Pancreatic Cancer Cells

2011 ◽  
Vol 176 (5) ◽  
pp. 565-574 ◽  
Author(s):  
Takahiro Yamauchi ◽  
Seiji Adachi ◽  
Ichiro Yasuda ◽  
Masanori Nakashima ◽  
Junji Kawaguchi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Egf Receptor ◽  
Human Pancreatic Cancer ◽  
Pancreatic Cancer Cells ◽  
Uvc Radiation

scholarly journals Cordycepin induces apoptosis in human pancreatic cancer cells via the mitochondrial-mediated intrinsic pathway and suppresses tumor growth in vivo

2018 ◽  
Vol Volume 11 ◽  
pp. 4479-4490 ◽  
Author(s):  
Yu Zhang ◽  
Xiao Xi Zhang ◽  
Rui Yan Yuan ◽  
Tai Ren ◽  
Ziyu Shao ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Human Pancreatic Cancer ◽  
Intrinsic Pathway ◽  
Pancreatic Cancer Cells

scholarly journals Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling

2016 ◽  
Vol 150 (2) ◽  
pp. 513-525.e10 ◽  
Author(s):  
Alexandra Matzke-Ogi ◽  
Katharina Jannasch ◽  
Marine Shatirishvili ◽  
Beatrix Fuchs ◽  
Sara Chiblak ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Models ◽  
Inhibition Of Tumor Growth ◽  
Tumor Growth And Metastasis
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