Curcumin combined with FAPαc vaccine elicits effective antitumor response by targeting indolamine-2,3-dioxygenase and inhibiting EMT induced by TNF-α in melanoma

Jiang, Guanmin; Xie, Wan‐Ying; Wang, Hongsheng; Du, Jie; Wu, Bingcheng; Xu, Wei; Liu, Huifang; Xiao, Ping; Liu, Zhigang; Li, Hongyan; Liu, Shuangquan; Yin, Wang; Zhang, Qiu-Gui; Liang, Jianping; Huang, Hui

doi:10.18632/oncotarget.4577

Cited by 40 publications

(38 citation statements)

References 29 publications

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“…Our experiments showed that the presence of diabetes led to elevated expression of TNF-α, IL-6 and p-NFκB in tumor tissues. These inflammatory factors promote tumor growth, exert anti-apoptotic activities and induce EMT [22–24]. Figures 5 and 8 show that SB203580 significantly downregulated these inflammatory factors in vitro and in vivo , inhibited tumor growth and metastasis and significantly prolonged the survival of mice with pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

et al. 2016

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Diabetes mellitus (DM) and its accompanying chronic inflammation promote tumor progression. p38 mitogen-activated protein kinase (MAPK) is an essential kinase for inflammation. The effects of p38 MAPK on epithelial-mesenchymal transition (EMT)-mediated diabetic pancreatic cancer metastasis remain unclear. Here, we demonstrate that p38 MAPK phosphorylation was significantly increased in pancreatic cancer cells treated with high glucose and in pancreatic tumors from diabetic animals. A p38 MAPK inhibitor significantly suppressed the proliferation and invasion of pancreatic cancer cells under high-glucose conditions. Moreover, p38 MAPK inhibition not only significantly decreased both the tumor volume monitored by magnetic resonance imaging and EMT-related metastasis but also increased the survival of diabetic mice bearing pancreatic tumors. Furthermore, the inflammation in diabetic animals bearing pancreatic tumors was also significantly lower after therapy. Collectively, our findings reveal that p38 MAPK inhibitors may provide a novel intervention strategy for diabetic pancreatic cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

et al. 2016

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“…Curcumin inhibited migration and decreased expression of MMP-2 and MMP-9 in A375 cells, and these effects were associated with decreased phosphorylation of JAK-2 and STAT-3 [175]. Curcumin also blocked TNF-α-induced upregulation of EMT markers in B16 cells; treated cells expressed less vimentin and more E-cadherin than controls [176]. Other studies have confirmed that treatment with curcumin decreased migration of B16F10 cells through collagen matrices via inhibition of MMPs [177].…”

Section: Phytochemicals With Known Anti-emt Propertiesmentioning

confidence: 99%

Potential therapeutic targets of epithelial–mesenchymal transition in melanoma

et al. 2017

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Melanoma is a cutaneous neoplastic growth of melanocytes with great potential to invade and metastasize, especially when not treated early and effectively. Epithelial-mesenchymal transition (EMT) is the process by which melanocytes lose their epithelial characteristics and acquire mesenchymal phenotypes. Mesenchymal protein expression increases the motility, invasiveness, and metastatic potential of melanoma. Many pathways play a role in promotion of mesenchymal protein expression including RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, and several others. Downstream effectors of these pathways induce expression of EMT transcription factors including Snail, Slug, Twist, and Zeb that promote repression of epithelial and induction of mesenchymal character. Emerging research has demonstrated that a variety of small molecule inhibitors as well as phytochemicals can influence the progression of EMT and may even reverse the process, inducing re-expression of epithelial markers. Phytochemicals are of particular interest as supplementary treatment options because of their relatively low toxicities and anti-EMT properties. Modulation of EMT signaling pathways using synthetic small molecules and phytochemicals is a potential therapeutic strategy for reducing the aggressive progression of metastatic melanoma. In this review, we discuss the emerging pathways and transcription factor targets that regulate EMT and evaluate potential synthetic small molecules and naturally occurring compounds that may reduce metastatic melanoma progression.

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“…We demonstrated that FAP α vaccine combined with curcumin lavage inhibits tumor growth and prolongs the survival of mice implanted with melanoma cells. The combination of a FAP α vaccine and curcumin stimulated FAP α antibody production and CD8+T cell-mediated killing of FAP α-expressing stromal cells without adverse reactive effects [9]. These results suggest that FAP α, a product preferentially expressed by CAFs, would be a more effective antigen to target in the setting of cancer immunotherapy.…”

Section: The Fap α-Targeted Immunotherapy Strategymentioning

confidence: 99%

“…Therefore, FAP α expressing cells are a non-redundant, immunosuppressive component of the TME [8]. Furthermore, it was reported that a FAP α vaccine combined with curcumin stimulates FAP α antibody production and CD8+ T cell-mediated killing of FAP α-expressing stromal cells and prolongs the survival of mice implanted with melanoma [9]. All of these results suggest that FAP α is an adaptive tumor-associated antigen useful for tumor immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

The application of the fibroblast activation protein α-targeted immunotherapy strategy

Jiang

et al. 2016

Oncotarget

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Cancer immunotherapy has primarily been focused on attacking tumor cells. However, given the close interaction between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME), CAF-targeted strategies could also contribute to an integrated cancer immunotherapy. Fibroblast activation protein α (FAP α) is not detectible in normal tissues, but is overexpressed by CAFs and is the predominant component of the stroma in most types of cancer. FAP α has both dipeptidyl peptidase and endopeptidase activities, cleaving substrates at a post-proline bond. When all FAP α-expressing cells (stromal and cancerous) are destroyed, tumors rapidly die. Furthermore, a FAP α antibody, FAP α vaccine, and modified vaccine all inhibit tumor growth and prolong survival in mouse models, suggesting FAP α is an adaptive tumor-associated antigen. This review highlights the role of FAP α in tumor development, explores the relationship between FAP α and immune suppression in the TME, and discusses FAP α as a potential immunotherapeutic target.

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Curcumin combined with FAPαc vaccine elicits effective antitumor response by targeting indolamine-2,3-dioxygenase and inhibiting EMT induced by TNF-α in melanoma

Abstract: ABSTRACT

Cited by 40 publications

References 29 publications

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

Diabetes mellitus stimulates pancreatic cancer growth and epithelial-mesenchymal transition-mediated metastasis via a p38 MAPK pathway

Potential therapeutic targets of epithelial–mesenchymal transition in melanoma

The application of the fibroblast activation protein α-targeted immunotherapy strategy

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