A Genome-Wide Screen in Mice To Identify Cell-Extrinsic Regulators of Pulmonary Metastatic Colonisation. Issue 6 (1st June 2020)

• Record Type: Journal Article
• Authors: van der Weyden, Louise; Swiatkowska, Agnieszka; Iyer, Vivek; Speak, Anneliese O; Adams, David J
• Is Part Of: G3. Volume 10:Issue 6(2020)
• Page Start: 1869
• Page End: 1877
• Publication Date: 2020-06-01
• Subjects: metastasis -- metastatic colonisation -- microenvironment -- B16-F10 -- lung -- mutant -- mouse; Genetics -- Research -- Periodicals; Genomics -- Periodicals; Genetics; Genomics; Genes; Genetics -- Research; Genomics; Electronic journals; Periodical; Periodicals; Fulltext; Internet Resources; Periodicals; 572.8
• DOI: 10.1534/g3.120.401128
• Languages: English
• ISSNs: 2160-1836

Abstract

Abstract: 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.