Cargando…
A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation
Metastatic colonization, whereby a disseminated tumor cell is able to survive and proliferate at a secondary site, involves both tumor cell-intrinsic and -extrinsic factors. To identify tumor cell-extrinsic (microenvironmental) factors that regulate the ability of metastatic tumor cells to effective...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263671/ https://www.ncbi.nlm.nih.gov/pubmed/32245826 http://dx.doi.org/10.1534/g3.120.401128 |
_version_ | 1783540834443984896 |
---|---|
author | van der Weyden, Louise Swiatkowska, Agnieszka Iyer, Vivek Speak, Anneliese O. Adams, David J. |
author_facet | van der Weyden, Louise Swiatkowska, Agnieszka Iyer, Vivek Speak, Anneliese O. Adams, David J. |
author_sort | van der Weyden, Louise |
collection | PubMed |
description | Metastatic colonization, whereby a disseminated tumor cell is able to survive and proliferate at a secondary site, involves both tumor cell-intrinsic and -extrinsic factors. To identify tumor cell-extrinsic (microenvironmental) factors that regulate the ability of metastatic tumor cells to effectively colonize a tissue, we performed a genome-wide screen utilizing the experimental metastasis assay on mutant mice. Mutant and wildtype (control) mice were tail vein-dosed with murine metastatic melanoma B16-F10 cells and 10 days later the number of pulmonary metastatic colonies were counted. Of the 1,300 genes/genetic locations (1,344 alleles) assessed in the screen 34 genes were determined to significantly regulate pulmonary metastatic colonization (15 increased and 19 decreased; P < 0.005 and genotype effect <-55 or >+55). While several of these genes have known roles in immune system regulation (Bach2, Cyba, Cybb, Cybc1, Id2, Igh-6, Irf1, Irf7, Ncf1, Ncf2, Ncf4 and Pik3cg) most are involved in a disparate range of biological processes, ranging from ubiquitination (Herc1) to diphthamide synthesis (Dph6) to Rho GTPase-activation (Arhgap30 and Fgd4), with no previous reports of a role in the regulation of metastasis. Thus, we have identified numerous novel regulators of pulmonary metastatic colonization, which may represent potential therapeutic targets. |
format | Online Article Text |
id | pubmed-7263671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-72636712020-06-08 A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation van der Weyden, Louise Swiatkowska, Agnieszka Iyer, Vivek Speak, Anneliese O. Adams, David J. G3 (Bethesda) Mutant Screen Report Metastatic colonization, whereby a disseminated tumor cell is able to survive and proliferate at a secondary site, involves both tumor cell-intrinsic and -extrinsic factors. To identify tumor cell-extrinsic (microenvironmental) factors that regulate the ability of metastatic tumor cells to effectively colonize a tissue, we performed a genome-wide screen utilizing the experimental metastasis assay on mutant mice. Mutant and wildtype (control) mice were tail vein-dosed with murine metastatic melanoma B16-F10 cells and 10 days later the number of pulmonary metastatic colonies were counted. Of the 1,300 genes/genetic locations (1,344 alleles) assessed in the screen 34 genes were determined to significantly regulate pulmonary metastatic colonization (15 increased and 19 decreased; P < 0.005 and genotype effect <-55 or >+55). While several of these genes have known roles in immune system regulation (Bach2, Cyba, Cybb, Cybc1, Id2, Igh-6, Irf1, Irf7, Ncf1, Ncf2, Ncf4 and Pik3cg) most are involved in a disparate range of biological processes, ranging from ubiquitination (Herc1) to diphthamide synthesis (Dph6) to Rho GTPase-activation (Arhgap30 and Fgd4), with no previous reports of a role in the regulation of metastasis. Thus, we have identified numerous novel regulators of pulmonary metastatic colonization, which may represent potential therapeutic targets. Genetics Society of America 2020-04-03 /pmc/articles/PMC7263671/ /pubmed/32245826 http://dx.doi.org/10.1534/g3.120.401128 Text en Copyright © 2020 van der Weyden et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Mutant Screen Report van der Weyden, Louise Swiatkowska, Agnieszka Iyer, Vivek Speak, Anneliese O. Adams, David J. A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation |
title | A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation |
title_full | A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation |
title_fullStr | A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation |
title_full_unstemmed | A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation |
title_short | A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation |
title_sort | genome-wide screen in mice to identify cell-extrinsic regulators of pulmonary metastatic colonisation |
topic | Mutant Screen Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263671/ https://www.ncbi.nlm.nih.gov/pubmed/32245826 http://dx.doi.org/10.1534/g3.120.401128 |
work_keys_str_mv | AT vanderweydenlouise agenomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT swiatkowskaagnieszka agenomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT iyervivek agenomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT speakannelieseo agenomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT adamsdavidj agenomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT vanderweydenlouise genomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT swiatkowskaagnieszka genomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT iyervivek genomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT speakannelieseo genomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation AT adamsdavidj genomewidescreeninmicetoidentifycellextrinsicregulatorsofpulmonarymetastaticcolonisation |