Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance

Erin, Nuray; Grahovac, Jelena; Brozović, Anamaria; Efferth, Thomas

doi:10.1016/j.drup.2020.100715

Cited by 345 publications

(224 citation statements)

References 440 publications

(445 reference statements)

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“…Low sensitivity of tumor cells to chemotherapy often correlates with their increased invasiveness [ 49 ]. To determine how the chemical structure of dendrons affects their impact on the invasiveness of phenotypically heterogeneous glioblastoma cells, we estimated the morphology and motility of the T98G cells treated by 15 and 13 .…”

Section: Resultsmentioning

confidence: 99%

“…Although further studies are necessary to comprehensively scrutinize these interrelations, 9a / 12a -induced selection of the “post-EMT” cells may account for the shifts in cell morphology. Epithelial-mesenchymal transition (EMT) results in increased motility/invasiveness of cancer cells and often increases their drug-resistance [ 49 ]. Even though glioblastoma is not an “epithelial” tumor, the corresponding process of “Glial-MT” may account for the decreased T98G cell reactivity to the compounds, thus facilitating their clonal expansion in stress conditions.…”

Section: Resultsmentioning

confidence: 99%

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Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties

et al. 2020

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(1) Background: Natural peptides supporting the innate immune system studied at the functional and mechanistic level are a rich source of innovative compounds for application in human therapy. Increasing evidence indicates that apart from antimicrobial activity, some of them exhibit selective cytotoxicity towards tumor cells. Their cationic, amphipathic structure enables interactions with the negatively-charged membranes of microbial or malignant cells. It can be modeled in 3D by application of dendrimer chemistry. (2) Methods: Here we presented design principles, synthesis and bioactivity of branched peptides constructed from ornithine (Orn) assembled as proline (Pro)- or histidine (His)-rich dendrons and dendrimers of the bola structure. The impact of the structure and amphipathic properties of dendrons/dendrimers on two glioblastoma cell lines U87 and T98G was studied with the application of proliferation, apoptosis and cell migration assays. Cell morphology/cytoskeleton architecture was visualized by immunofluorescence microscopy. (3) Results: Dimerization of dendrons into bola dendrimers enhanced their bioactivity. Pro- and His-functionalized bola dendrimers displayed cytostatic activity, even though differences in the responsiveness of U87 and T98G cells to these compounds indicate that their bioactivity depends not only on multiple positive charge and amphipathic structure but also on cellular phenotype. (4) Conclusion: Ornithine dendrons/dendrimers represent a group of promising anti-tumor agents and the potential tools to study interrelations between drug bioactivity, its chemical properties and tumor cells’ phenotype.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties

et al. 2020

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“…Resistance to anticancer drugs is a crucial problem that limits the effectiveness of chemotherapy regimens ( 43 ). Resistance generally develops with long-term exposure to the drug ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine resistance in triple‑negative breast cancer cells can be reverted by <em>Drosophila melanogaster</em> deoxyribonucleoside kinase in the nucleus or cytosol

Zhao

Jiang

et al. 2020

Oncol Lett

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The development of drug resistance to chemotherapeutic agents has consistently presented a challenge in terms of the treatment of patients with triple-negative breast cancer (TNBC). In the present study, gemcitabine (dFdC)-resistant TNBC cells were established, and the effects of lentivirus-deoxyribonucleoside kinase (dNK) and a mutated form of dNK (lentivirus-dNKmut) on reversing the acquired drug resistance in dFdC-resistant TNBC cells were explored. Quantitative PCR and western blotting experiment results suggested that Drosophila melanogaster (Dm)-dNK was stably expressed in the lentivirus-infected MDA-MB-231 and MDA-MB-231R cells in the nucleus or cytosol, and autoradiography experiments revealed similar levels of enzymatic activity in the cells expressing dNK or dNKmut. In vitro cytotoxicity assay revealed that the IC 50 values of dFdC were decreased 30~50-fold in the dFdC-resistant MDA-MB-231 cells following lentiviral transfection with dNK or dNKmut, and this effect was associated with a significantly increased rate of apoptosis compared with the cells transfected with the negative control lentivirus. In conclusion, Dm-dNK in the nucleus or cytosol may be a potential candidate for reversing acquired dFdC resistance in TNBC cells, which may form the basis of novel strategies for the treatment of patients with drug-resistant TNBC.

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“…Exosomes, which are small lipid vesicles containing proteins and genetic material, are secreted by different types of cells into the TME, inducing pro-invasion and survival signaling in cancer cells [ 87 ]. In addition, inflammatory factors in the TME mediate epithelial–mesenchymal transition (EMT), metastasis, and resistance through the expansion and recruitment of CAFs and immune cells such as macrophages [ 88 ]. Together, the TME and tumor cells crosstalk to support cancer cell survival ( Figure 2 ).…”

Section: Apc Loss and Tumor Microenvironment-derived Chemoresistanmentioning

confidence: 99%

Wnt-Independent and Wnt-Dependent Effects of APC Loss on the Chemotherapeutic Response

Stefanski

Prosperi

2020

IJMS

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Resistance to chemotherapy occurs through mechanisms within the epithelial tumor cells or through interactions with components of the tumor microenvironment (TME). Chemoresistance and the development of recurrent tumors are two of the leading factors of cancer-related deaths. The Adenomatous Polyposis Coli (APC) tumor suppressor is lost in many different cancers, including colorectal, breast, and prostate cancer, and its loss correlates with a decreased overall survival in cancer patients. While APC is commonly known for its role as a negative regulator of the WNT pathway, APC has numerous binding partners and functional roles. Through APC’s interactions with DNA repair proteins, DNA replication proteins, tubulin, and other components, recent evidence has shown that APC regulates the chemotherapy response in cancer cells. In this review article, we provide an overview of some of the cellular processes in which APC participates and how they impact chemoresistance through both epithelial- and TME-derived mechanisms.

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Tumor microenvironment and epithelial mesenchymal transition as targets to overcome tumor multidrug resistance

Cited by 345 publications

References 440 publications

Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties

Bioinspired Bola-Type Peptide Dendrimers Inhibit Proliferation and Invasiveness of Glioblastoma Cells in a Manner Dependent on Their Structure and Amphipathic Properties

Gemcitabine resistance in triple‑negative breast cancer cells can be reverted by <em>Drosophila melanogaster</em> deoxyribonucleoside kinase in the nucleus or cytosol

Wnt-Independent and Wnt-Dependent Effects of APC Loss on the Chemotherapeutic Response

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