American Association for Cancer Research
00085472can152662-sup-155992_1_supp_3322683_41d3v6.docx (22.79 kB)

supplementary tables from In Vivo Visualization and Characterization of Epithelial–Mesenchymal Transition in Breast Tumors

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journal contribution
posted on 2023-03-31, 00:12 authored by Zhen Zhao, Xiaoping Zhu, Kemi Cui, James Mancuso, Richard Federley, Kari Fischer, Gao-jun Teng, Vivek Mittal, Dingcheng Gao, Hong Zhao, Stephen T.C. Wong

Table 1: Distribution of the GFP+ cells in whole tumor central vs peripheral area and tumor lobule central vs peripheral area. Table 2: RNAseq gene expressions of growth factor receptors in sorted RFP+ and GFP+ cells.





The activation of the epithelial-to-mesenchymal transition (EMT) program is a critical step in cancer progression and metastasis, but visualization of this process at the single-cell level, especially in vivo, remains challenging. We established an in vivo approach to track the fate of tumor cells based on a novel EMT-driven fluorescent color switching breast cancer mouse model and intravital two-photon laser scanning microscopy. Specifically, the MMTV-PyMT, Rosa26-RFP-GFP, and Fsp1-Cre triple transgenic mouse model was used to monitor the conversion of RFP-positive epithelial cells to GFP-positive mesenchymal cells in mammary tumors under the control of the Fsp1 (ATL1) promoter, a gate-keeper of EMT initiation. RFP-positive cells were isolated from the tumors, sorted, and transplanted into mammary fat pads of SCID mice to monitor EMT during breast tumor formation. We found that the conversion from RFP- to GFP-positive and spindle-shaped cells was a gradual process, and that GFP-positive cells preferentially localized close to blood vessels, independent of tumor size. Furthermore, cells undergoing EMT expressed high levels of the HGF receptor, c-Met, and treatment of RFP-positive cells with the c-Met inhibitor, cabozantinib, suppressed the RFP-to-GFP conversion in vitro. Moreover, administration of cabozantinib to mice with palpable RFP-positive tumors resulted in a silent EMT phenotype whereby GFP-positive cells exhibited reduced motility, leading to suppressed tumor growth. In conclusion, our imaging technique provides a novel opportunity for visualizing tumor EMT at the single-cell level and may help to reveal the intricacies underlying tumor dynamics and treatment responses. Cancer Res; 76(8); 2094–104. ©2016 AACR.

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