Bulk tumour cell migration in lung carcinomas might be more common than epithelial-mesenchymal transition and be differently regulated

Zacharias, Martin; Brčić, Luka; Eidenhammer, Sylvia; Popper, Helmut

doi:10.1186/s12885-018-4640-y

Cited by 37 publications

(29 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…EpCAM+, Cytokeratins+, E-cad+, Vimentin+, N-cad+, O-cad+, CD133+ [85] CTCs from women with metastatic BT Hybrid EMT Cytokeratins+, Vimentin+, N-cad+ [85] ESCC PT or MLN specimen from ESCC patients E-cad+, N-cad+, vimentin+ [86] CTC from early stage breast cancer patients stemness TWIST1+, CD44+, ALDH1+, EpCAM+ [87] Breast cancer samples from primary site and metastatic lymph nodes of breast cancer patients Co-expression of E/M markers E-cad+, vimentin+ [88] Human primary colorectal cancer specimen Cytokeratin+, vimentin+ [89] Primary HGSOC tumour E-cad+, vimentin+ [90] Primary AC, SCC tumours Vimentin+/cytokeratin+, E-cad+/N-cad+ [91] Abbreviations: ANKRD1, ankyrin repeat domain-containing protein 1; AOX1, aldehyde oxidase 1; COL3A1, collagen Type III α1 Chain; FGF2, fibroblast growth factor; LAMC2, laminin subunit γ 2; MME, membrane metallo-endopeptidase.…”

Section: Clinical Evidence Of Partial Emt In Human Cancersmentioning

confidence: 99%

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

et al. 2020

View full text Add to dashboard Cite

Epithelial mesenchymal transition (EMT) is a complex process through which epithelial (E) cells lose their adherens junctions, transform into mesenchymal (M) cells and attain motility, leading to metastasis at distant organs. Nowadays, the concept of EMT has shifted from a binary phase of interconversion of pure E to M cells and vice versa to a spectrum of E/M transition states preferably coined as hybrid/partial/intermediate EMT. Hybrid EMT, being a plastic transient state, harbours cells which co-express both E and M markers and exhibit high tumourigenic properties, leading to stemness, metastasis, and therapy resistance. Several preclinical and clinical studies provided the evidence of co-existence of E/M phenotypes. Regulators including transcription factors, epigenetic regulators and phenotypic stability factors (PSFs) help in maintaining the hybrid state. Computational and bioinformatics approaches may be excellent for identifying new factors or combinations of regulatory elements that govern the different EMT transition states. Therapeutic intervention against hybrid E/M cells, though few, may evolve as a rational strategy against metastasis and drug resistance. This review has attempted to present the recent advancements on the concept and regulation of the process of hybrid EMT which generates hybrid E/M phenotypes, evidence of intermediate EMT in both preclinical and clinical setup, impact of partial EMT on promoting tumourigenesis, and future strategies which might be adapted to tackle this phenomenon.

show abstract

Section: Clinical Evidence Of Partial Emt In Human Cancersmentioning

confidence: 99%

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Mild increase in hepatocytic mitosis (orange arrow) was observed in the liver of mice treated with free drugs. The abnormal histological symptoms detected (white arrow) in the lung and liver of mice treated with saline and empty Na-DOC-hyd+G4.5 biomaterial indicated the possibility of metastasis in mice not treated with any therapeutic drugs [ 65 , 66 ]. In contrast, organs collected specifically from mice treated with the Na-DOC-hyd-RESV+G4.5-DOX formulation did not show any significant histological abnormality, confirming the biosafety of the drug carriers, as well as RESV.…”

Section: Resultsmentioning

confidence: 99%

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

et al. 2020

View full text Add to dashboard Cite

Maximizing the antitumor efficacy of doxorubicin (DOX) with a new drug delivery strategy is always desired in the field of biomedical science. Because the clinical applications of DOX in the treatment of cancer is limited by the side effects related to the dose. Herein, we report the co-loading of DOX and resveratrol (RESV) using an injectable in situ formed sodium deoxycholate hydrogel (Na-DOC-hyd) at the pH of the tumor extracellular microenvironment. The sequential, controlled, and sustained release of RESV and DOX for synergistic antitumor effects was confirmed by entrapping G4.5-DOX in the RESV-loaded Na-DOC hydrogel (Na-DOC-hyd-RESV). The synergistic antitumor activity of Na-DOC-hyd-RESV+G4.5-DOX was assessed on HeLa cell xenograft tumor in BALB/c nude mice. In the MTT biocompatibility assay, both the G4.5 PAMAM dendrimer and Na-DOC-hyd exhibited negligible cytotoxicity up to the highest dose of 2.0 mg mL−1 in HeLa, MDA-MB-231, and HaCaT cells. The release profiles of DOX and RESV from the Na-DOC-hyd-RESV+G4.5-DOX confirmed the relatively rapid release of RESV (70.43 ± 1.39%), followed by that of DOX (54.58 ± 0.62%) at pH 6.5 in the 7 days of drug release studies. A single intratumoral injection of Na-DOC-hyd-RESV+G4.5-DOX maximally suppressed tumor growth during the 28 days of the treatment period. Na-DOC-hyd-RESV+G4.5-DOX did not cause any histological damage in the major visceral organs. Therefore, this Na-DOC-hydrogel for dual drugs (DOX and RESV) delivery at the pH of the tumor extracellular microenvironment is a promising, safe, and effective combination for antitumor chemotherapy.

show abstract

“…Our study might suggest that, although emt is one of the most important causes of tumour metastasis, other factors could play crucial role in lung adenocarcinoma. Bulk tumour-cell migration has been reported to potentially be more common than emt in lung carcinoma, and tumour cells were found to be able to migrate without changing to the mesenchymal phenotype called "epithelial migration type" 36 . Some studies have shown that reduction in E-cadherin expression is related to a decrease in sensitivity to epidermal growth factor receptor tyrosine kinase inhibitor and to EGFR status 37,38 , results that are not consistent with the present study.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of Epithelial–Mesenchymal Transition–Related Molecules in Lung Adenocarcinoma

Zhang

Wang

Gao³

et al. 2019

Current Oncology

View full text Add to dashboard Cite

Background Epithelial–mesenchymal transition (emt) refers to the biologic process in which epithelial cells are transformed into interstitial phenotypes by specific pathways. This transition plays an important biologic role in the process by which epithelium-derived malignant tumour cells acquire the ability to migrate and invade. We explored the relationship between emt-associated molecules and patient-related clinical factors to determine whether any clinical characteristics could be used as biomarkers for emt-related protein alterations in lung cancer—especially lung adenocarcinoma.Methods Tumour specimens were collected from 80 patients with lung adenocarcinoma who underwent surgery or lung biopsy, with 4 patients being evaluated a 2nd time after re-biopsy. Expression of emt-related proteins, including E-cadherin and vimentin, was evaluated by immunohistochemistry. We analyzed the relationship between clinicopathologic characteristics and expression level of the emt markers.Results Positive expression of E-cadherin was observed in 63 patients (79%), and vimentin, in 46 patients (57.5%). No significant relationships between E-cadherin or vimentin expression and smoking history, sex, age, driving gene mutations, or cell differentiation were identified. A significant correlation was observed between vimentin expression and pathologic stage. Of the 4 patients who were evaluated a 2nd time after re-biopsy, 3 showed the same emt-related protein expression status as in the first analysis. In the remaining patient, E-cadherin had changed completely.Conclusions Clinicopathologic factors in cancer patients did not help to diagnose emt status in lung adenocarcinoma; however, TNM stage might be associated with vimentin expression.

show abstract

Bulk tumour cell migration in lung carcinomas might be more common than epithelial-mesenchymal transition and be differently regulated

Cited by 37 publications

References 48 publications

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

Emerging Concepts of Hybrid Epithelial-to-Mesenchymal Transition in Cancer Progression

Bioinspired Composite, pH-Responsive Sodium Deoxycholate Hydrogel and Generation 4.5 Poly(amidoamine) Dendrimer Improves Cancer Treatment Efficacy via Doxorubicin and Resveratrol Co-Delivery

Clinical Significance of Epithelial–Mesenchymal Transition–Related Molecules in Lung Adenocarcinoma

Contact Info

Product

Resources

About