Irreversible inhibition of Δ16HER2 is necessary to suppress Δ16HER2-positive breast carcinomas resistant to Lapatinib

Tilio, Martina; Gambini, Valentina; Wang, Junbiao; Garulli, Chiara; Kalogris, Cristina; Andreani, Cristina; Bartolacci, Caterina; Zabaleta, María Eléxpuru; Pietrella, Lucia; Hysi, Albana; Iezzi, Manuela; Belletti, Barbara; Orlando, Fiorenza; Provinciali, Mauro; Galeazzi, Roberta; Marchini, Cristina; Amici, Augusto

doi:10.1016/j.canlet.2016.07.028

Cited by 24 publications

(29 citation statements)

References 42 publications

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“…CAM6 cells have been established from Δ16HER2 mice and can be considered the in vitro counterpart of Δ16HER2 mammary tumors [17]. After 24 hours’ incubation, despite high resveratrol concentrations resulted in reduced cell viability, low-range resveratrol concentrations (20-30 μM) promoted cell proliferation of both CAM6 and BT474 cells (Figure 3a and 3b), mimicking the in vivo resveratrol effect.…”

Section: Resultsmentioning

confidence: 83%

“…CAM6 cells, a Δ16HER2-expressing epithelial tumor cell line derived from a mammary carcinoma spontaneously arisen in a Δ16HER2 female [17] and BT474 cell line were maintained in DMEM (Lonza) supplemented with 10% FBS (Gibco, Life Technologies) and 1% penicillin-streptomycin (Gibco, Life Technologies). Cells were cultured at 37°C under humidified atmosphere with 5% CO2.…”

Section: Resultsmentioning

confidence: 99%

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Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor

Andreani

Bartolacci

Wijnant

et al. 2017

Aging

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The phytoestrogen resveratrol has been reported to possess cancer chemo-preventive activity on the basis of its effects on tumor cell lines and xenograft or carcinogen-inducible in vivo models. Here we investigated the effects of resveratrol on spontaneous mammary carcinogenesis using Δ16HER2 mice as HER2+/ERα+ breast cancer model. Instead of inhibiting tumor growth, resveratrol treatment (0.0001% in drinking water; daily intake of 4μg/mouse) shortened tumor latency and enhanced tumor multiplicity in Δ16HER2 mice. This in vivo tumor-promoting effect of resveratrol was associated with up-regulation of Δ16HER2 and down-regulation of ERα protein levels and was recapitulated in vitro by murine (CAM6) and human (BT474) tumor cell lines. Our results demonstrate that resveratrol, acting as a proteasome inhibitor, leads to Δ16HER2 accumulation which favors the formation of Δ16HER2/HER3 heterodimers. The consequential activation of downstream mTORC1/p70S6K/4EBP1 pathway triggers cancer growth and proliferation. This study provides evidence that resveratrol mechanism of action (and hence its effects) depends on the intrinsic molecular properties of the cancer model under investigation, exerting a tumor-promoting effect in luminal B breast cancer subtype models.

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Section: Resultsmentioning

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor

Andreani

Bartolacci

Wijnant

et al. 2017

Aging

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“…Every year, breast cancer causes over 500,000 deaths. Recently, the advent of targeted therapies that include tyrosine kinase inhibitors (TKIs), such as lapatinib and anti-HER2 antibodies (such as trastuzumab), have considerably improved the overall survival and time-to-disease progression values in HER2+ breast cancer patients 3 . Although encouraging progress has been made in recent years due to the development of targeted therapy, the prognosis for breast cancer remains poor due to invasion and metastasis.…”

Section: Introductionmentioning

confidence: 99%

β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers

Yang

Zhou

et al. 2017

Sci Rep

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NQO1 is a FAD-binding protein that can form homodimers and reduce quinones to hydroquinones, and a growing body of evidence currently suggests that NQO1 is dramatically elevated in solid cancers. Here, we demonstrated that NQO1 was elevated in breast cancer and that its expression level was positively correlated with invasion and reduced disease free survival (DFS) and overall survival (OS) rates. Next, we found that β-lapachone exerted significant anti-proliferation and anti-metastasis effects in breast cancer cell lines due to its effects on NQO1 expression. Moreover, we revealed that the anti-cancer effects of β-lapachone were mediated by the inactivation of the Akt/mTOR pathway. In conclusion, these results demonstrated that NQO1 could be a useful prognostic biomarker for patients with breast cancer, and its bioactivatable drug, β-lapachone represented a promising new development and an effective strategy for indicating the progression of NQO1-positive breast cancers.

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“…91 Success in treating breast cancers is often reliant on the expression of certain receptors. 96 One group created a DNA vaccination that encoded the extracellular and transmembrane domains of Δ16HER2 and demonstrated that following prophylactic immunization, mice were 100% protected from challenge with Δ16HER2-expressing tumor cells for up to 100 days. 92 There are currently a number of FDA-approved monoclonal antibody treatments aimed at HER2, but they often need to be combined with chemotherapy which comprises the patient's immune system and is generally toxic to all cell types.…”

Section: Filamentous Phagementioning

confidence: 99%

“…95 In fact, it is thought that resistance to monoclonal antibody treatments may be due to inability to bind to this variant form of HER2. 96 One group created a DNA vaccination that encoded the extracellular and transmembrane domains of Δ16HER2 and demonstrated that following prophylactic immunization, mice were 100% protected from challenge with Δ16HER2-expressing tumor cells for up to 100 days. 97 The group next employed a model where transgenic mice express human Δ16HER2 and spontaneously develop mammary carcinomas.…”

Section: Filamentous Phagementioning

confidence: 99%

Phage display as a tool for vaccine and immunotherapy development

Hess

Jewell

2019

Bioengineering & Transla Med

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Bacteriophages, or phages, are viruses that specifically infect bacteria and coopt the cellular machinery to create more phage proteins, eventually resulting in the release of new phage particles. Phages are heavily utilized in bioengineering for applications ranging from tissue engineering scaffolds to immune signal delivery. Of specific interest to vaccines and immunotherapies, phages have demonstrated an ability to activate both the innate and adaptive immune systems. The genome of these viral particles can be harnessed for DNA vaccination, or the surface proteins can be exploited for antigen display. More specifically, genes that encode an antigen of interest can be spliced into the phage genome, allowing antigenic proteins or peptides to be displayed by fusion to phage capsid proteins. Phages therefore present antigens to immune cells in a highly ordered and repetitive manner. This review discusses the use of phage with adjuvanting activity as antigen delivery vehicles for vaccination against infectious disease and cancer. K E Y W O R D S bacteriophage, biomaterials, drug delivery, immunology, nanotechnology, phage display, vaccine 1 | INTRODUCTION Bacteriophages, or phages, are prokaryotic viruses that specifically infect bacteria, and are the most abundant life form on earth. 1 Phages were first discovered in the early 20th century and noted for their antibacterial activity. The practice of administering phages (i.e., phage therapy) to patients suffering from bacterial infections began shortly after their discovery, but was controversial largely due to lack of mechanistic knowledge and variable success rates. In fact, the treatment was largely abandoned upon the discovery of antibiotics. 2 Research in this field was reenergized, however, following the development of phage display systems in 1985. 3 George Smith, a chemist at the University of Missouri, demonstrated fusion of peptides to the outer (i.e., capsid) proteins of phages enabling surface display. This work, for which Smith shared a Nobel Prize in 2018, laid the ground work for affinity selection, epitope mapping, and antibody discovery. Since this time, phages have been an important tool for the bioengineering field, exploited for a range of applications including theranostics, 4 batteries, 5,6 drug delivery, 7 and vaccine development. 1Phages are one of many nanotechnologies being investigated for these applications. This review will focus on the advantages that phages provide to the nanomedicine field, specifically vaccination and immunotherapy. Nanomedicine ranges from diagnostics to treatments and relies on the fields of biomedical and chemical engineering,

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Irreversible inhibition of Δ16HER2 is necessary to suppress Δ16HER2-positive breast carcinomas resistant to Lapatinib

Cited by 24 publications

References 42 publications

Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor

Resveratrol fuels HER2 and ERα-positive breast cancer behaving as proteasome inhibitor

β-lapachone suppresses tumour progression by inhibiting epithelial-to-mesenchymal transition in NQO1-positive breast cancers

Phage display as a tool for vaccine and immunotherapy development

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