Endocanalicular transendothelial crossing (ETC): A novel intravasation mode used by HEK-EBNA293-VEGF-D cells during the metastatic process in a xenograft model

Autor: D. Dallatana, Attilio Corradi, Federico Armando, Rosanna Di Lecce, Anna Maria Cantoni, Ewan R. Cameron, Matteo Zanfabro, Guerino Lombardi, Maria Luisa Arcari, Giacomo Azzali, Luca Ferrari, Maura Ferrari, Paolo Lunghi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Pathology
Cell
Mice
SCID
Epithelium
Metastasis
Diagnostic Radiology
Mice
0302 clinical medicine
Animal Cells
Neoplasms
Basic Cancer Research
Breast Tumors
Medicine and Health Sciences
Electron Microscopy
Materials
Tomography
Microscopy
Multidisciplinary
Invasive Tumors
Radiology and Imaging
Endothelial stem cell
medicine.anatomical_structure
Lymphatic system
Oncology
030220 oncology & carcinogenesis
Lymphatic Metastasis
Physical Sciences
Medicine
Cellular Types
Anatomy
Organic Materials
Research Article
medicine.medical_specialty
Epithelial-Mesenchymal Transition
Imaging Techniques
Science
Materials Science
Neuroimaging
Research and Analysis Methods
03 medical and health sciences
Diagnostic Medicine
Cell Line
Tumor
Breast Cancer
medicine
Animals
Humans
Epithelial–mesenchymal transition
business.industry
HEK 293 cells
Intravasation
Biology and Life Sciences
Endothelial Cells
Cancers and Neoplasms
Epithelial Cells
Cell Biology
medicine.disease
Computed Axial Tomography
Disease Models
Animal
030104 developmental biology
Biological Tissue
Waxes
Cancer cell
Transmission Electron Microscopy
business
Neoplasm Transplantation
Neuroscience
Zdroj: PLoS ONE, Vol 15, Iss 10, p e0239932 (2020)
PLoS ONE
ISSN: 1932-6203
Popis: In cancer metastasis, intravasation of the invasive tumor cell (TCi) represents one of the most relevant events. During the last years, models regarding cancer cell intravasation have been proposed, such as the “endocanalicular transendothelial crossing” (ETC) theory. This theory describes the interplay between two adjacent endothelial cells and the TCi or a leukocyte during intravasation. Two endothelial cells create a channel with their cell membranes, in which the cell fits in without involving endothelial cell intercellular junctions, reaching the lumen through a transendothelial passage. In the present study, ten SCID mice were subcutaneously xenotransplanted with the HEK-EBNA293-VEGF-D cell line and euthanized after 35 days. Post-mortem examinations were performed and proper specimens from tumors were collected. Routine histology and immunohistochemistry for Ki-67, pAKT, pERK, ZEB-1, TWIST-1, F-actin, E-cadherin and LYVE-1 were performed followed by ultrastructural serial sections analysis. A novel experimental approach involving Computed Tomography (CT) combined with 3D digital model reconstruction was employed. The analysis of activated transcription factors supports that tumor cells at the periphery potentially underwent an epithelial-to-mesenchymal transition (EMT)-like process. Topographical analysis of LYVE-1 immunolabeled lymphatics revealed a peritumoral localisation. TEM investigations of the lymphatic vessels combined with 3D digital modelling enhanced the understanding of the endotheliocytes behavior during TCi intravasation, clarifying the ETC theory. Serial ultrastructural analysis performed within tumor periphery revealed numerous cells during the ETC process. Furthermore, this study demonstrates that ETC is an intravasation mode more frequently used by the TCi than by leukocytes during intravasation in the HEK-EBNA293-VEGF-D xenograft model and lays down the potential basis for promising future studies regarding intravasation blocking therapy.
Databáze: OpenAIRE
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