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

Autor: Armando F; Department of Veterinary Science, Pathology Unit, University of Parma, Parma, Italy., Ferrari L; Department of Veterinary Science, Pathology Unit, University of Parma, Parma, Italy., Arcari ML; Department of Medicine and Surgery, University of Parma, Parma, Italy., Azzali G; Department of Medicine and Surgery, University of Parma, Parma, Italy., Dallatana D; Department of Medicine and Surgery, University of Parma, Parma, Italy., Ferrari M; Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'B. Ubertini', Unit of Brescia, Brescia, Italy., Lombardi G; Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna 'B. Ubertini', Unit of Brescia, Brescia, Italy., Zanfabro M; Practitioner, 3D Veterinary Printing Project, Parma, Italy.; Department of Veterinary Science, Diagnostic Imaging Unit, University of Parma, Parma, Italy., Di Lecce R; Department of Veterinary Science, Pathology Unit, University of Parma, Parma, Italy., Lunghi P; Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma,Parma, Italy.; Centre for Molecular and Translational Oncology, University of Parma, Parma, Italy., Cameron ER; School of Veterinary Medicine, University of Glasgow, Glasgow, Scotland., Cantoni AM; Department of Veterinary Science, Pathology Unit, University of Parma, Parma, Italy., Corradi A; Department of Veterinary Science, Pathology Unit, University of Parma, Parma, Italy.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Oct 21; Vol. 15 (10), pp. e0239932. Date of Electronic Publication: 2020 Oct 21 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0239932
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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