Dissecting metastasis using preclinical models and methods

Neutrophil Nanodecoys Inhibit Tumor Metastasis by Blocking the Interaction between Tumor Cells and Neutrophils

“…This is similar to the results of Szczerba et al, who found that depleting neutrophils with Anti Ly6G did not prevent lung metastasis caused by direct intravenous injection of tumor cells . This may be due to the fact that the direct injection of cancer cells into the circulation induces lung metastasis mainly by the rapid trapping of numerous cells within the microvasculature of the lung minutes after injection, which only represents the late phases of the invasion–metastasis cascade and organ colonization but fails to capture the earlier stages of the metastatic process, such as local invasion and intravasation, and does not fully model the normal course of hematogenous spread. , …”

“…13 This may be due to the fact that the direct injection of cancer cells into the circulation induces lung metastasis mainly by the rapid trapping of numerous cells within the microvasculature of the lung minutes after injection, which only represents the late phases of the invasion−metastasis cascade and organ colonization but fails to capture the earlier stages of the metastatic process, such as local invasion and intravasation, and does not fully model the normal course of hematogenous spread. 36,38 These findings show that aNEM NPs do not affect primary tumor growth but hold a strong antimetastatic effect in both orthotopic and lymph node metastasis models of 4T1 cancer cells. However, aNEM NPs have only a slightly antimetastatic effect in the intravenous injection of 4T1 cells induced lung metastasis model, suggesting that they are unable to prevent the entrapment and implantation of intravenously injected numerous 4T1 cells in the lung microvasculature.…”

“…To explore the antimetastatic efficacy of aNEM NPs in vivo, we established a highly metastatic tumor model by orthotopically implanting GFP-4T1 cells into the mammary fat pad of mice, which recapitulates the entire metastatic cascade, including the early steps of migration, invasion and extravasation. 36 Seven days after the injection of GFP-4T1 cells, we treated mice with various formulations. In addition to PLA NPs and naNEM NPs groups, we also used Ly6G antibodies (Anti-Ly6G) as positive controls, as it has been shown to reduce tumor metastasis by depleting neutrophils.…”

“…Here, we further verified whether the antimetastatic effect of aNEM NPs was attributed to inhibition of neutrophil−tumor interaction. Since orthotopic metastasis model recapitulates the entire metastatic cascade, including the early steps of migration, invasion, and extravasation, 36 we further employed this model to systemically study the effect of aNEM NPs on the tumor cells−neutrophils interaction from primary tumor to circulation to premetastasis niches.…”

Combinatorialin vivogenome editing identifies widespread epistasis during lung tumorigenesis

“…Cancer genome sequencing has cataloged somatic alterations at the genome-wide level and identified many putative driver genes 14,15 . However, identifying recurrent genomic alterations does not necessarily reveal their functional importance to cancer growth, and the impact of gene inactivation remains difficult to glean from cancer genome sequencing data alone 16–18 . Tumor suppressor gene alterations in particular are diverse and have non-random patterns of co-occurrence, suggesting underlying genetic interactions 14,19–21 .…”