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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Shared Science Publishers OG
2018-10-01
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| Series: | Cell Stress |
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| Online Access: | http://www.cell-stress.com/researcharticles/intravital-imaging-tumor-screen-used-to-identify-novel-metastasis-blocking-therapeutic-targets/ |
| _version_ | 1818025846203482112 |
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| author | Konstantin Stoletov Lian Willetts Perrin H. Beatty John D. Lewis |
| author_facet | Konstantin Stoletov Lian Willetts Perrin H. Beatty John D. Lewis |
| author_sort | Konstantin Stoletov |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T04:22:36Z |
| format | Article |
| id | doaj.art-ef2ad0988ea74504ba6fa5a2c0313cfe |
| institution | Directory Open Access Journal |
| issn | 2523-0204 |
| language | English |
| last_indexed | 2024-12-10T04:22:36Z |
| publishDate | 2018-10-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Cell Stress |
| spelling | doaj.art-ef2ad0988ea74504ba6fa5a2c0313cfe2022-12-22T02:02:22ZengShared Science Publishers OGCell Stress2523-02042018-10-0121027527810.15698/cst2018.10.159Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targetsKonstantin Stoletov0Lian Willetts1Perrin H. Beatty2John D. Lewis3Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1.Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1.Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1.Department of Oncology, University of Alberta, Edmonton, Alberta, Canada, T6G 2E1.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.http://www.cell-stress.com/researcharticles/intravital-imaging-tumor-screen-used-to-identify-novel-metastasis-blocking-therapeutic-targets/ex ovo chick embryo modelfluorescence time-lapse intravital imaginghigh throughput sequencingintravasationmetastatic cancershRNA librarytherapeutic targets |
| spellingShingle | Konstantin Stoletov Lian Willetts Perrin H. Beatty John D. Lewis Intravital imaging tumor screen used to identify novel metastasis-blocking therapeutic targets Cell Stress ex ovo chick embryo model fluorescence time-lapse intravital imaging high throughput sequencing intravasation metastatic cancer shRNA library 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 | ex ovo chick embryo model fluorescence time-lapse intravital imaging high throughput sequencing intravasation metastatic cancer shRNA library therapeutic targets |
| url | http://www.cell-stress.com/researcharticles/intravital-imaging-tumor-screen-used-to-identify-novel-metastasis-blocking-therapeutic-targets/ |
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