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      Changes in cell shape are correlated with metastatic potential in murine and human osteosarcomas

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          ABSTRACT

          Metastatic cancer cells for many cancers are known to have altered cytoskeletal properties, in particular to be more deformable and contractile. Consequently, shape characteristics of more metastatic cancer cells may be expected to have diverged from those of their parental cells. To examine this hypothesis we study shape characteristics of paired osteosarcoma cell lines, each consisting of a less metastatic parental line and a more metastatic line, derived from the former by in vivo selection. Two-dimensional images of four pairs of lines were processed. Statistical analysis of morphometric characteristics shows that shape characteristics of the metastatic cell line are partly overlapping and partly diverged from the parental line. Significantly, the shape changes fall into two categories, with three paired cell lines displaying a more mesenchymal-like morphology, while the fourth displaying a change towards a more rounded morphology. A neural network algorithm could distinguish between samples of the less metastatic cells from the more metastatic cells with near perfect accuracy. Thus, subtle changes in shape carry information about the genetic changes that lead to invasiveness and metastasis of osteosarcoma cancer cells.

          Abstract

          Summary: Human and murine invasive osteosarcoma cancer cell lines, developed by selection in vivo from a less invasive parental line, show distinguishable differences in shape from the parental line that fall into two categories: more mesenchymal or more amoeboid.

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          Tensional homeostasis and the malignant phenotype.

          Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.
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            A scaled conjugate gradient algorithm for fast supervised learning

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              Cell adhesion and signalling by cadherins and Ig-CAMs in cancer.

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                Author and article information

                Journal
                Biol Open
                Biol Open
                BIO
                biolopen
                Biology Open
                The Company of Biologists Ltd
                2046-6390
                15 March 2016
                12 February 2016
                12 February 2016
                : 5
                : 3
                : 289-299
                Affiliations
                [1 ]School of Biomedical Engineering, Colorado State University , Fort Collins, CO 80523, USA
                [2 ]College of Veterinary Medicine and Biomedical Sciences, Colorado State University , Fort Collins, CO 80523, USA
                [3 ]Department of Chemical and Biological Engineering, Colorado State University , Fort Collins, CO 80523, USA
                [4 ]Department of Biology, Colorado State University , Fort Collins, CO 80523, USA
                [5 ]Department of Statistics, Colorado State University , Fort Collins, CO 80523, USA
                Author notes
                [*]

                These authors contributed equally to this work

                []Author for correspondence ( ashokp@ 123456engr.colostate.edu )
                Article
                BIO013409
                10.1242/bio.013409
                4810736
                26873952
                bd5eb6bf-1a05-48c0-9648-2f1caae3838c
                © 2016. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 12 July 2015
                : 20 January 2016
                Funding
                Funded by: Directorate for Mathematical and Physical Sciences, http://dx.doi.org/10.13039/100000086;
                Award ID: PHY-1151454
                Categories
                Research Article

                Life sciences
                cell shape,cytoskeleton,invasiveness,machine learning,metastasis,morphometrics
                Life sciences
                cell shape, cytoskeleton, invasiveness, machine learning, metastasis, morphometrics

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