scholarly journals Molecular Imaging of Inducible VEGF Expression and Tumor Progression in a Breast Cancer Model

2017 ◽  
Vol 42 (1) ◽  
pp. 407-415 ◽  
Author(s):  
Lu Liang ◽  
Zhiwei Yue ◽  
Wei Du ◽  
Yang Li ◽  
Hongyan Tao ◽  
...  

Background: Tumor derived vascular endothelial growth factor (VEGF) can stimulate proliferation and migration of endothelial cells and recruit endothelial progenitor cells into tumors for vascular formation via a paracrine manner. Now increasing evidence suggests that VEGF also serves as an autocrine factor promoting cell survival and tumor angiogenesis. Real time visualization of VEGF activity in the early stages of tumor formation using molecular imaging will provide unprecedented insight into the biological processes of cancer. Methods: The mouse breast cancer cell line 4T1 was transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF and renilla luciferase (Rluc). This was used to quantitatively image conditional switching of VEGF by bioluminescence imaging (BLI) under the control of systemic administration of doxycycline. Simultaneously, 4T1 cells were labelled with the double fusion reporter gene (Fluc-eGFP) to establish a breast cancer model. Results: We found that inducible VEGF could promote proliferation and attenuate apoptosis due to oxidative stress in an autocrine manner in vitro. In vivo studies revealed that induction of VEGF expression during early tumor development not only dramatically enhanced tumor growth but also increased tumor angiogenesis as visualized by BLI. Finally, immunohistochemistry staining confirmed that inducing VEGF expression promoted cell survival and tumor neovascularization. Conclusion: Together the inducible bidirectional tetracycline (Bi-Tet) co-expression system combined with the dual bioluminescence imaging (BLI) system provides a platform to investigate a target gene’s role in the pathologic process of cancer and facilitates noninvasive monitoring of biological responses in real time.

2013 ◽  
Vol 142 (1) ◽  
pp. 9-18 ◽  
Author(s):  
Giselle V. Ripoll ◽  
Juan Garona ◽  
Marina Pifano ◽  
Hernan G. Farina ◽  
Daniel E. Gomez ◽  
...  

2014 ◽  
Vol 4 (1) ◽  
pp. 17 ◽  
Author(s):  
Erik Samén ◽  
Li Lu ◽  
Jan Mulder ◽  
Jan-Olov Thorell ◽  
Peter Damberg ◽  
...  

2015 ◽  
Vol 122 (03) ◽  
Author(s):  
FJ Möller ◽  
K Wende ◽  
O Zierau ◽  
MC Bosland ◽  
MH Muders ◽  
...  

2021 ◽  
pp. 2100008
Author(s):  
Hamilton Kakwere ◽  
Hua Zhang ◽  
Elizabeth S. Ingham ◽  
Marina Nura‐Raie ◽  
Spencer K. Tumbale ◽  
...  

2021 ◽  
Vol 38 (1) ◽  
pp. 1099-1110
Author(s):  
Leonardo Bianchi ◽  
Rachael Mooney ◽  
Yvonne R. Cornejo ◽  
Emiliano Schena ◽  
Jacob M. Berlin ◽  
...  

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 499
Author(s):  
Tracy W. Liu ◽  
Seth T. Gammon ◽  
David Piwnica-Worms

Intravital microscopic imaging (IVM) allows for the study of interactions between immune cells and tumor cells in a dynamic, physiologically relevant system in vivo. Current IVM strategies primarily use fluorescence imaging; however, with the advances in bioluminescence imaging and the development of new bioluminescent reporters with expanded emission spectra, the applications for bioluminescence are extending to single cell imaging. Herein, we describe a molecular imaging window chamber platform that uniquely combines both bioluminescent and fluorescent genetically encoded reporters, as well as exogenous reporters, providing a powerful multi-plex strategy to study molecular and cellular processes in real-time in intact living systems at single cell resolution all in one system. We demonstrate that our molecular imaging window chamber platform is capable of imaging signaling dynamics in real-time at cellular resolution during tumor progression. Importantly, we expand the utility of IVM by modifying an off-the-shelf commercial system with the addition of bioluminescence imaging achieved by the addition of a CCD camera and demonstrate high quality imaging within the reaches of any biology laboratory.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jiayue-Clara Jiang ◽  
Joseph A. Rothnagel ◽  
Kyle R. Upton

AbstractWhile transposons are generally silenced in somatic tissues, many transposons escape epigenetic repression in epithelial cancers, become transcriptionally active and contribute to the regulation of human gene expression. We have developed a bioinformatic pipeline for the integrated analysis of transcription factor binding and transcriptomic data to identify transposon-derived promoters that are activated in specific diseases and developmental states. We applied this pipeline to a breast cancer model, and found that the L1PA2 transposon subfamily contributes abundant regulatory sequences to co-ordinated transcriptional regulation in breast cancer. Transcription factor profiling demonstrates that over 27% of L1PA2 transposons harbour co-localised binding sites of functionally interacting, cancer-associated transcription factors in MCF7 cells, a cell line used to model breast cancer. Transcriptomic analysis reveals that L1PA2 transposons also contribute transcription start sites to up-regulated transcripts in MCF7 cells, including some transcripts with established oncogenic properties. In addition, we verified the utility of our pipeline on other transposon subfamilies, as well as on leukemia and lung carcinoma cell lines. We demonstrate that the normally quiescent regulatory activities of transposons can be activated and alter the cancer transcriptome. In particular, the L1PA2 subfamily contributes abundant regulatory sequences, and likely plays a global role in modulating breast cancer transcriptional regulation. Understanding the regulatory impact of L1PA2 on breast cancer genomes provides additional insights into cancer genome regulation, and may provide novel biomarkers for disease diagnosis, prognosis and therapy.


Sign in / Sign up

Export Citation Format

Share Document