Show simple item record

dc.contributor.authorFifis, T
dc.contributor.authorNguyen, L
dc.contributor.authorMalcontenti-Wilson, C
dc.contributor.authorChan, LS
dc.contributor.authorCosta, PLN
dc.contributor.authorDaruwalla, J
dc.contributor.authorNikfarjam, M
dc.contributor.authorMuralidharan, V
dc.contributor.authorWaltham, M
dc.contributor.authorThompson, EW
dc.contributor.authorChristophi, C
dc.date.accessioned2021-02-16T22:06:11Z
dc.date.available2021-02-16T22:06:11Z
dc.date.issued2013-10-01
dc.identifier.citationFifis, T., Nguyen, L., Malcontenti-Wilson, C., Chan, L. S., Costa, P. L. N., Daruwalla, J., Nikfarjam, M., Muralidharan, V., Waltham, M., Thompson, E. W. & Christophi, C. (2013). Treatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor. CANCER MEDICINE, 2 (5), pp.595-610. https://doi.org/10.1002/cam4.109.
dc.identifier.issn2045-7634
dc.identifier.urihttp://hdl.handle.net/11343/261735
dc.description.abstractEpithelial to mesenchymal transition (EMT) is considered an important mechanism in tumor resistance to drug treatments; however, in vivo observation of this process has been limited. In this study we demonstrated an immediate and widespread EMT involving all surviving tumor cells following treatment of a mouse model of colorectal liver metastases with the vascular disruptive agent OXi4503. EMT was characterized by significant downregulation of E-cadherin, relocation and nuclear accumulation of β-catenin as well as significant upregulation of ZEB1 and vimentin. Concomitantly, significant temporal upregulation in hypoxia and the pro-angiogenic growth factors hypoxia-inducible factor 1-alpha, hepatocyte growth factor, vascular endothelial growth factor and transforming growth factor-beta were seen within the surviving tumor. The process of EMT was transient and by 5 days after treatment tumor cell reversion to epithelial morphology was evident. This reversal, termed mesenchymal to epithelial transition (MET) is a process implicated in the development of new metastases but has not been observed in vivo histologically. Similar EMT changes were observed in response to other antitumor treatments including chemotherapy, thermal ablation, and antiangiogenic treatments in our mouse colorectal metastasis model and in a murine orthotopic breast cancer model after OXi4503 treatment. These results suggest that EMT may be an early mechanism adopted by tumors in response to injury and hypoxic stress, such that inhibition of EMT in combination with other therapies could play a significant role in future cancer therapy.
dc.languageEnglish
dc.publisherWILEY-BLACKWELL
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleTreatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor
dc.typeJournal Article
dc.identifier.doi10.1002/cam4.109
melbourne.affiliation.departmentSurgery (Austin & Northern Health)
melbourne.affiliation.departmentSurgery (St Vincent's)
melbourne.affiliation.departmentBusiness & Economics
melbourne.affiliation.department
melbourne.affiliation.facultyCollected Works
melbourne.source.titleCancer Medicine
melbourne.source.volume2
melbourne.source.issue5
melbourne.source.pages595-610
melbourne.identifier.nhmrc400190
dc.rights.licenseCC BY
melbourne.elementsid738470
melbourne.contributor.authorNguyen, Linh
melbourne.contributor.authorMALCONTENTI-WILSON, CATERINA
melbourne.contributor.authorCosta, Patricia
melbourne.contributor.authorNikfarjam, Mehrdad
melbourne.contributor.authorMuralidharan, Vijayaragavan
melbourne.contributor.authorWaltham, Mark
melbourne.contributor.authorThompson, Erik
melbourne.contributor.authorChristophi, Christopher
melbourne.contributor.authorFifis, Theodora
melbourne.contributor.authorCHAN, LISA
dc.identifier.eissn2045-7634
melbourne.identifier.fundernameidNHMRC, 400190
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record