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Updated: Jan 23, 2026

Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
Konstantin Stoletov1, Lian Willetts1, Perrin H Beatty1
1Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1.
Abstract:
Cancer cell motility is a key driver of metastasis. Although the intravasation of cancer cells into the blood stream is highly dependent on their motility and metastatic dissemination is the primary cause of cancer related deaths, current therapeutic strategies do not target the genes and proteins that are essential for cell motility. A primary reason for this is because the identification of cell motility-related genes that are relevant in vivo requires the visualization of metastatic lesions forming in an appropriate in vivo model. The cancer research community has lacked an in vivo and intravital metastatic cancer model that could be imaged as motility developed, in real-time. To address this, we developed a novel quantitative in vivo screening platform based on intravital imaging in shell-less ex ovo chick embryos. We applied this imaging approach to screen a human genome-wide short hairpin RNA library (shRNA) versus the highly motile head and neck cancer cells (HEp3 cell line) introduced into the chorioallantoic membrane (CAM) of chick embryos and identified multiple novel in vivo cancer cell motility-associated genes. When the expression of several of the identified genes was inhibited in the HEp3 tumors, we observed a nearly total block of spontaneous cancer metastasis.
Insights
Researchers developed a new imaging platform to study cancer cell metastasis in real-time. This approach identified novel genes crucial for cancer cell motility and blocking them halted metastasis.
Area of Science:
- Oncology
- Cell Biology
- Biotechnology
Background:
- Cancer cell motility is a critical factor in metastasis, the primary cause of cancer-related mortality.
- Current therapies do not target genes essential for cell motility due to limitations in visualizing metastasis in vivo.
- There is a need for advanced in vivo models that allow real-time imaging of cancer cell motility and metastasis.
Purpose of the Study:
- To develop a novel in vivo screening platform for identifying genes associated with cancer cell motility.
- To apply this platform to discover new therapeutic targets for blocking cancer metastasis.
Main Methods:
- Developed a quantitative in vivo screening platform using intravital imaging in shell-less ex ovo chick embryos.
- Screened a human genome-wide short hairpin RNA library against highly motile head and neck cancer cells (HEp3) in the chick embryo chorioallantoic membrane (CAM).
Main Results:
- Identified multiple novel genes associated with in vivo cancer cell motility.
- Inhibiting the expression of identified genes in HEp3 tumors resulted in a near-complete blockage of spontaneous cancer metastasis.
Conclusions:
- The developed chick embryo model provides a powerful tool for real-time imaging and screening of cancer cell motility in vivo.
- The identified genes represent promising novel therapeutic targets for preventing cancer metastasis.
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