In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 2316-2316
Abstract:
During malignant progression, primary tumor cells switch from proliferative to invasive phenotypes and switch again at low frequency to form proliferating metastases. The acquisition of the invasive phenotype through epithelial-mesenchymal-transition (E-M-T) is a critical step in tumor progression, as is the mesenchymal-epithelial-transition (M-E-T) reverting to a proliferative colony or metastases. To study the mechanism(s) underlying phenotypic switching, we isolated HGF/SF-inducible invasive mesenchymal (M) and non-invasive epithelial (E) subclones from prostate and ovarian carcinoma cell lines based on three dimensional branching morphogenesis assays. We show that invasive M subclones can be generated from originally homogeneous non-invasive E subclones and phenotype switching occurs with loss of E-Cadherin and concomitant gain of Met signaling. By contrast, tumor xenograph formed by invasive M subclones partially revert to epithelial phenotype with gain of E-Cadherin and loss of HGF/SF-Met signaling, suggesting an interplay between E-Cadherin and HGF/SF-Met signaling in regulating reversible phenotypic switching. We have further studied the mechanisms regulating phenotypic switching. Our results explicate how intrinsic alteration in tumor cell properties (E-M-T) and extrinsic signals from microenvironment (HGF/SF) interact in regulating tumor phenotypic switching. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2316.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM10-2316
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2010
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
