Show simple item record

dc.contributor.authorTang, Xin
dc.contributor.authorKuhlenschmidt, Theresa B
dc.contributor.authorLi, Qian
dc.contributor.authorAli, Shahjahan
dc.contributor.authorLezmi, Stephane
dc.contributor.authorChen, Hong
dc.contributor.authorPires-Alves, Melissa
dc.contributor.authorLaegreid, William W
dc.contributor.authorSaif, Taher A
dc.contributor.authorKuhlenschmidt, Mark S
dc.date.accessioned2014-08-27T09:42:47Z
dc.date.available2014-08-27T09:42:47Z
dc.date.issued2014-05-29
dc.identifier.citationTang X, Kuhlenschmidt TB, Li Q, Ali S, Lezmi S, et al. (2014) A mechanically-induced colon cancer cell population shows increased metastatic potential. Mol Cancer 13: 131. doi:10.1186/1476-4598-13-131.
dc.identifier.issn14764598
dc.identifier.pmid24884630
dc.identifier.doi10.1186/1476-4598-13-131
dc.identifier.urihttp://hdl.handle.net/10754/325255
dc.description.abstractBackground: Metastasis accounts for the majority of deaths from cancer. Although tumor microenvironment has been shown to have a significant impact on the initiation and/or promotion of metastasis, the mechanism remains elusive. We previously reported that HCT-8 colon cancer cells underwent a phenotypic transition from an adhesive epithelial type (E-cell) to a rounded dissociated type (R-cell) via soft substrate culture, which resembled the initiation of metastasis. The objective of current study was to investigate the molecular and metabolic mechanisms of the E-R transition.Methods: Global gene expressions of HCT-8 E and R cells were measured by RNA Sequencing (RNA-seq); and the results were further confirmed by real-time PCR. Reactive oxygen species (ROS), anoikis resistance, enzyme activity of aldehyde dehydrogenase 3 family, member A1 (ALDH3A1), and in vitro invasion assay were tested on both E and R cells. The deformability of HCT-8 E and R cells was measured by atomic force microscopy (AFM). To study the in vivo invasiveness of two cell types, athymic nude mice were intra-splenically injected with HCT-8 E or R cells and sacrificed after 9 weeks. Incidences of tumor development and metastasis were histologically evaluated and analyzed with Fisher's exact test.Results: Besides HCT-8, E-R transition on soft substrates was also seen in three other cancer cell lines (HCT116, SW480 colon and DU145 prostate cancer). The expression of some genes, such as ALDH3A1, TNS4, CLDN2, and AKR1B10, which are known to play important roles in cancer cell migration, invasion, proliferation and apoptosis, were increased in HCT-8 R cells. R cells also showed higher ALDH3A1 enzyme activity, higher ROS, higher anoikis resistance, and higher softness than E cells. More importantly, in vitro assay and in vivo animal models revealed that HCT-8 R cells were more invasive than E cells.Conclusions: Our comprehensive comparison of HCT-8 E and R cells revealed differences of molecular, phenotypical, and mechanical signatures between the two cell types. To our knowledge, this is the first study that explores the molecular mechanism of E-R transition, which may greatly increase our understanding of the mechanisms of cancer mechanical microenvironment and initiation of cancer metastasis. 2014 Tang et al.; licensee BioMed Central Ltd.
dc.language.isoen
dc.publisherSpringer Nature
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.urihttp://creativecommons.org/licenses/by/2.0
dc.subjectCancer biomarkers
dc.subjectIn vitro cancer microenvironment
dc.subjectInvasiveness
dc.subjectMechanotransduction
dc.subjectMetastasis
dc.subjectPolyacrylamide hydrogel
dc.subjectaldehyde dehydrogenase
dc.subjectaldehyde dehydrogenase 3a1
dc.subjectbone morphogenetic protein 4
dc.subjectepithelial derived neutrophil activating factor 78
dc.subjectHLA E antigen
dc.subjectreactive oxygen metabolite
dc.subjectunclassified drug
dc.subjectanimal experiment
dc.subjectanimal tissue
dc.subjectapoptosis
dc.subjectatomic force microscopy
dc.subjectcancer cell culture
dc.subjectcell migration
dc.subjectcldn2 gene
dc.subjectcolon cancer
dc.subjectenzyme activity
dc.subjectepithelial mesenchymal transition
dc.subjectgene expression
dc.subjecthuman cell
dc.subjectin vivo study
dc.subjectmarker gene
dc.subjectmetastasis potential
dc.subjectmouse
dc.subjectprotein expression
dc.subjectreal time polymerase chain reaction
dc.subjectRNA sequence
dc.subjectTNS4 gene
dc.subjecttumor invasion
dc.subjectAnimalia
dc.subjectMus musculus
dc.titleA mechanically-induced colon cancer cell population shows increased metastatic potential
dc.typeArticle
dc.identifier.journalMolecular Cancer
dc.identifier.pmcidPMC4072622
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Mechanical Science and Engineering, College of Engineering, University of Illinois at Urbana-Champaign, 206 W. Green St, Urbana 61802, IL, United States
dc.contributor.institutionDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Ave, Urbana 61802, IL, United States
dc.contributor.institutionDepartment of Food Science and Human Nutrition and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, 905 S. Goodwin Ave, Urbana 61802, IL, United States
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personAli, Shahjahan
refterms.dateFOA2018-06-13T14:41:13Z


Files in this item

Thumbnail
Name:
Article-Molecular_-A_mechanic-2014.pdf
Size:
2.949Mb
Format:
PDF
Description:
Article - Full Text

This item appears in the following Collection(s)

Show simple item record

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Except where otherwise noted, this item's license is described as This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.