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

Abstract

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.

• Authors: Lu Liang, Zhiwei Yue, Wei Du, Yang Li, Hongyan Tao, Di Wang, Ran Wang, Ziwei Huang, Ningning He, Xiaoyan Xie, Zhongchao Han, Na Liu, Zongjin Li
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 42 Issue 1 Pg. 407-415 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 28558368 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Vascular Endothelial Growth Factor A
• Hydrogen Peroxide
• Doxycycline

Topics

• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (diagnosis, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Disease Progression
• Doxycycline (toxicity)
• Female
• Gene Expression Regulation, Neoplastic
• Genes, Reporter
• Humans
• Hydrogen Peroxide (toxicity)
• Mice
• Mice, Inbred BALB C
• Microscopy, Fluorescence
• Neovascularization, Pathologic (prevention & control)
• Optical Imaging
• Oxidative Stress (drug effects)
• Vascular Endothelial Growth Factor A (genetics, metabolism)