Recombinant immunotoxin anti-c-Met/PE38KDEL inhibits proliferation and promotes apoptosis of gastric cancer cells

Backgroundc-MET is an oncogene protein that plays important role in gastric carcinogenesis and has been introduced as a prognostic marker and potential therapeutic target. The aim of this study was to evaluate the frequency of c-MET overexpression and its relationship with clinicopathological variables in gastric cancer of Iranian population using tissue microarray.MethodsIn a cross sectional study, representative paraffin blocks of 130 patients with gastric carcinoma treated by curative gastrectomy during a 2 years period of 2008–2009 in two university hospitals in Tehran-Iran were collected in tissue microarray and c-MET expression was studied by immunohistochemical staining.ResultsFinally 124 cases were evaluated, constituted of 99 male and 25 female with the average age of 61.5 years. In 71% (88/124) of tumors, c-MET high expression was found. c-MET high expression was more associated with intestinal than diffuse tumor type (P = 0.04), deeper tumor invasion, pT3 and pT4 versus pT1 and pT2 (P = 0.014), neural invasion (P = 0.002) and advanced TNM staging, stage 3 and 4 versus stage 1 and2 (P = 0.044). The c-MET high expression was not associated with age, sex, tumor location, differentiation grade and distant metastasis, but relative associations with lymph node metastasis (P = 0.065) and vascular invasion (P = 0.078) were observed.Conclusionsc-MET oncogene protein was frequently overexpressed in Iranian gastric carcinomas and it was related to clinicopathological characteristics such as tumor type, depth of invasion, neural invasion and TNM staging. It can also support the idea that c-MET is a potential marker for target therapy in Iranian gastric cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9744598757151429

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“…Until now many new anti-c-MET drugs have been invented and most are in preclinical and clinical testing [34,36]. …”

Section: Discussionmentioning

confidence: 99%

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

et al. 2012

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“…Upregulation of c-MET may increase the expression and phosphorylation of STAT3, wherein the activated STAT3 directly regulates genes involved in proliferation (including cyclin D1, c-Myc, p53 and p21), survival (including Bcl-2, Bcl-xL, MCL1 apoptosis regulator and survivin), metastasis (including MMP2 and MMP9) and angiogenesis (including vascular endothelial growth factor) in numerous types of cancer. The role of c-MET/STAT3 signaling in gastric cancer has been previously discussed in multiple studies (25,26), including a previous study from our group (27). To further examine whether c-Met/STAT3 signaling may serve a key role in IL-10-induced tumor-promoting behaviors of gastric cancer cells, the expression levels of c-Met, and of downstream effectors STAT3, MMP9 and caspase-3, were examined following treatment with CAM-conditioned media.…”

Section: Discussionmentioning

confidence: 84%

IL‑10 secreted by cancer‑associated macrophages regulates proliferation and invasion in gastric cancer cells via c‑Met/STAT3 signaling

et al. 2019

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Gastric cancer is one of the most common types of human cancer, and it is additionally one of the leading causes of cancer-associated mortality worldwide. Previous studies have suggested that interleukin (IL)-10 may contribute to the pathogenesis of gastric cancer. However, the underlying mechanisms remain unclear. In the present study, it was observed that the expression of IL-10 was significantly upregulated in gastric tumor tissues and serum samples of patients with gastric cancer. Furthermore, IL-10 was increased in the cell culture supernatant of cancer-associated macrophages (CAMs). Treatment with cell culture supernatant from CAMs induced a significant increase in proliferation and migration, while it suppressed apoptosis, in MGC-803 and BGC-823 gastric cancer cells. Notably, application of an inhibitory IL-10 antibody partially blocked the cell culture supernatant of CAM-induced oncogenic effects. RNA-sequencing analysis was then performed to identify the differentially expressed genes in MGC-803 cells treated with IL-10. Based on the sequencing results and in vitro analysis, it was demonstrated that IL-10-induced carcinogenic behaviors in MGC-803 cells were potentially mediated by activation of the c-Met/STAT3 signaling pathway. In conclusion, the present results demonstrated that IL-10 secreted by CAMs may be involved in the pathogenesis of gastric cancer, suggesting that IL-10 may serve as a potential therapeutic target for the treatment of gastric cancer.

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“…The value of each plate represented the direct correlation with the number of living cells. Values of the measured WST-8 were used to calculate values of IR with Equation (1) [ 40 ]: IR = (1 − (A − B)/(C − B)) × 100 where A = the value in the treated samples; B = the value in the blank samples; and C = the value in the control samples. This test was done in quadruple and repeated three times.…”

Section: Methodsmentioning

confidence: 99%

Multi-Walled Carbon Nanotubes Promote Cementoblast Differentiation and Mineralization through the TGF-β/Smad Signaling Pathway

Zhu

Xiao

et al. 2015

IJMS

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Excretion of cementum by cementoblasts on the root surface is a process indispensable for the formation of a functional periodontal ligament. This study investigated whether carboxyl group-functionalized multi-walled carbon nanotubes (MWCNT-COOH) could enhance differentiation and mineralization of mammalian cementoblasts (OCCM-30) and the possible signaling pathway involved in this process. Cementoblasts were incubated with various doses of MWCNT-COOH suspension. Cell viability was detected, and a scanning electron microscopy (SEM) observed both the nanomaterials and the growth of cells cultured with the materials. Alizarin red staining was used to investigate the formation of calcium deposits. Real-time PCR and western blot were used to detect cementoblast differentiation and the underlying mechanisms through the expression of the osteogenic genes and the downstream effectors of the TGF-β/Smad signaling. The results showed that 5 µg/mL MWCNT-COOH had the most obvious effects on promoting differentiation without significant toxicity. Alp, Ocn, Bsp, Opn, Col1 and Runx2 gene expression was up-regulated. Smad2 and Smad3 mRNA was up-regulated, while Smad7 was first down-regulated on Day 3 and later up-regulated on Day 7. The elevated levels of phospho-Smad2/3 were also confirmed by western blot. In sum, the MWCNT-COOH promoted cementoblast differentiation and mineralization, at least partially, through interactions with the TGF-β/Smad pathway.

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Recombinant immunotoxin anti-c-Met/PE38KDEL inhibits proliferation and promotes apoptosis of gastric cancer cells

Cited by 12 publications

References 25 publications

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

The clinicopathologic association of c-MET overexpression in Iranian gastric carcinomas; an immunohistochemical study of tissue microarrays

IL‑10 secreted by cancer‑associated macrophages regulates proliferation and invasion in gastric cancer cells via c‑Met/STAT3 signaling

Multi-Walled Carbon Nanotubes Promote Cementoblast Differentiation and Mineralization through the TGF-β/Smad Signaling Pathway

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