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3 Publications visible to you, out of a total of 3

Abstract

Not specified

Author: Amruta Damle-Vartak

Date Published: 1st Dec 2018

Publication Type: Not specified

Abstract (Expand)

Dynamic polarisation of tumour cells is essential for metastasis. While the role of polarisation during dedifferentiation and migration is well established, polarisation of metastasising tumour cells during phases of detachment has not been investigated. Here we identify and characterise a type of polarisation maintained by single cells in liquid phase termed single-cell (sc) polarity and investigate its role during metastasis. We demonstrate that sc polarity is an inherent feature of cells from different tumour entities that is observed in circulating tumour cells in patients. Functionally, we propose that the sc pole is directly involved in early attachment, thereby affecting adhesion, transmigration and metastasis. In vivo, the metastatic capacity of cell lines correlates with the extent of sc polarisation. By manipulating sc polarity regulators and by generic depolarisation, we show that sc polarity prior to migration affects transmigration and metastasis in vitro and in vivo.

Authors: A. Lorentzen, P. F. Becker, J. Kosla, M. Saini, K. Weidele, P. Ronchi, C. Klein, M. J. Wolf, F. Geist, B. Seubert, M. Ringelhan, D. Mihic-Probst, K. Esser, M. Roblek, F. Kuehne, G. Bianco, T. O'Connor, Q. Muller, K. Schuck, S. Lange, D. Hartmann, S. Spaich, O. Gross, J. Utikal, S. Haferkamp, M. R. Sprick, A. Damle-Vartak, A. Hapfelmeier, N. Huser, U. Protzer, A. Trumpp, D. Saur, N. Vartak, C. A. Klein, B. Polzer, L. Borsig, M. Heikenwalder

Date Published: 2nd Mar 2018

Publication Type: Not specified

Abstract (Expand)

UNLABELLED: Cholestasis is a common complication in liver diseases that triggers a proliferative response of the biliary tree. Bile duct ligation (BDL) is a frequently used model of cholestasis in rodents. To determine which changes occur in the three-dimensional (3D) architecture of the interlobular bile duct during cholestasis, we used 3D confocal imaging, surface reconstructions, and automated image quantification covering a period up to 28 days after BDL. We show a highly reproducible sequence of interlobular duct remodeling, where cholangiocyte proliferation initially causes corrugation of the luminal duct surface, leading to an approximately five-fold increase in surface area. This is analogous to the function of villi in the intestine or sulci in the brain, where an expansion of area is achieved within a restricted volume. The increase in surface area is further enhanced by duct branching, branch elongation, and loop formation through self-joining, whereby an initially relatively sparse mesh surrounding the portal vein becomes five-fold denser through elongation, corrugation, and ramification. The number of connections between the bile duct and the lobular bile canalicular network by the canals of Hering decreases proportionally to the increase in bile duct length, suggesting that no novel connections are established. The diameter of the interlobular bile duct remains constant after BDL, a response that is qualitatively distinct from that of large bile ducts, which tend to enlarge their diameters. Therefore, volume enhancement is only due to net elongation of the ducts. Because curvature and tortuosity of the bile duct are unaltered, this enlargement of the biliary tree is caused by branching and not by convolution. CONCLUSION: BDL causes adaptive remodeling that aims at optimizing the intraluminal surface area by way of corrugation and branching.

Authors: N. Vartak, A. Damle-Vartak, B. Richter, O. Dirsch, U. Dahmen, S. Hammad, J. G. Hengstler

Date Published: 27th Nov 2015

Publication Type: Not specified

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