A mechanically-induced colon cancer cell population shows increased metastatic potential

Handle URI:
http://hdl.handle.net/10754/325255
Title:
A mechanically-induced colon cancer cell population shows increased metastatic potential
Authors:
Tang, Xin; Kuhlenschmidt, Theresa B; Li, Qian; Ali, Shahjahan; Lezmi, Stephane; Chen, Hong; Pires-Alves, Melissa; Laegreid, William W; Saif, Taher A; Kuhlenschmidt, Mark S
Abstract:
Background: 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.
Citation:
Tang 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.
Publisher:
Springer Nature
Journal:
Molecular Cancer
Issue Date:
29-May-2014
DOI:
10.1186/1476-4598-13-131
PubMed ID:
24884630
PubMed Central ID:
PMC4072622
Type:
Article
ISSN:
14764598
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorTang, Xinen
dc.contributor.authorKuhlenschmidt, Theresa Ben
dc.contributor.authorLi, Qianen
dc.contributor.authorAli, Shahjahanen
dc.contributor.authorLezmi, Stephaneen
dc.contributor.authorChen, Hongen
dc.contributor.authorPires-Alves, Melissaen
dc.contributor.authorLaegreid, William Wen
dc.contributor.authorSaif, Taher Aen
dc.contributor.authorKuhlenschmidt, Mark Sen
dc.date.accessioned2014-08-27T09:42:47Z-
dc.date.available2014-08-27T09:42:47Z-
dc.date.issued2014-05-29en
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.en
dc.identifier.issn14764598en
dc.identifier.pmid24884630en
dc.identifier.doi10.1186/1476-4598-13-131en
dc.identifier.urihttp://hdl.handle.net/10754/325255en
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.en
dc.language.isoenen
dc.publisherSpringer Natureen
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.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectCancer biomarkersen
dc.subjectIn vitro cancer microenvironmenten
dc.subjectInvasivenessen
dc.subjectMechanotransductionen
dc.subjectMetastasisen
dc.subjectPolyacrylamide hydrogelen
dc.subjectaldehyde dehydrogenaseen
dc.subjectaldehyde dehydrogenase 3a1en
dc.subjectbone morphogenetic protein 4en
dc.subjectepithelial derived neutrophil activating factor 78en
dc.subjectHLA E antigenen
dc.subjectreactive oxygen metaboliteen
dc.subjectunclassified drugen
dc.subjectanimal experimenten
dc.subjectanimal tissueen
dc.subjectapoptosisen
dc.subjectatomic force microscopyen
dc.subjectcancer cell cultureen
dc.subjectcell migrationen
dc.subjectcldn2 geneen
dc.subjectcolon canceren
dc.subjectenzyme activityen
dc.subjectepithelial mesenchymal transitionen
dc.subjectgene expressionen
dc.subjecthuman cellen
dc.subjectin vivo studyen
dc.subjectmarker geneen
dc.subjectmetastasis potentialen
dc.subjectmouseen
dc.subjectprotein expressionen
dc.subjectreal time polymerase chain reactionen
dc.subjectRNA sequenceen
dc.subjectTNS4 geneen
dc.subjecttumor invasionen
dc.subjectAnimaliaen
dc.subjectMus musculusen
dc.titleA mechanically-induced colon cancer cell population shows increased metastatic potentialen
dc.typeArticleen
dc.identifier.journalMolecular Canceren
dc.identifier.pmcidPMC4072622en
dc.eprint.versionPublisher's Version/PDFen
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 Statesen
dc.contributor.institutionDepartment of Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, 2001 S. Lincoln Ave, Urbana 61802, IL, United Statesen
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 Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorAli, Shahjahanen

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