Cargando…

Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets

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 t...

Descripción completa

Detalles Bibliográficos
Autores principales: Stoletov, Konstantin, Willetts, Lian, Beatty, Perrin H., Lewis, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Shared Science Publishers OG 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551637/
https://www.ncbi.nlm.nih.gov/pubmed/31225451
http://dx.doi.org/10.15698/cst2018.10.159
_version_ 1783424424235499520
author Stoletov, Konstantin
Willetts, Lian
Beatty, Perrin H.
Lewis, John D.
author_facet Stoletov, Konstantin
Willetts, Lian
Beatty, Perrin H.
Lewis, John D.
author_sort Stoletov, Konstantin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6551637
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Shared Science Publishers OG
record_format MEDLINE/PubMed
spelling pubmed-65516372019-06-20 Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets Stoletov, Konstantin Willetts, Lian Beatty, Perrin H. Lewis, John D. Cell Stress Microreview 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. Shared Science Publishers OG 2018-10-04 /pmc/articles/PMC6551637/ /pubmed/31225451 http://dx.doi.org/10.15698/cst2018.10.159 Text en Copyright: © 2018 Stoletov et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
spellingShingle Microreview
Stoletov, Konstantin
Willetts, Lian
Beatty, Perrin H.
Lewis, John D.
Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
title Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
title_full Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
title_fullStr Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
title_full_unstemmed Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
title_short Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
title_sort intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets
topic Microreview
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551637/
https://www.ncbi.nlm.nih.gov/pubmed/31225451
http://dx.doi.org/10.15698/cst2018.10.159
work_keys_str_mv AT stoletovkonstantin intravitalimagingtumorscreenusedtoidentifynovelmetastasisblockingtherapeutictargets
AT willettslian intravitalimagingtumorscreenusedtoidentifynovelmetastasisblockingtherapeutictargets
AT beattyperrinh intravitalimagingtumorscreenusedtoidentifynovelmetastasisblockingtherapeutictargets
AT lewisjohnd intravitalimagingtumorscreenusedtoidentifynovelmetastasisblockingtherapeutictargets