The CCL7 Knockout UM-UC-3 Polyclonal Cells represent a CRISPR/Cas9-edited polyclonal knockout cell population derived from the UM-UC-3 human bladder carcinoma cell line. This product carries a targeted disruption of the CCL7 gene, resulting in a loss-of-function model suitable for investigating chemokine-dependent signaling networks. The polyclonal format maintains the inherent genetic heterogeneity of the parental line, avoiding clonal selection artifacts and enabling robust population-level studies of CCL7-deficient phenotypes.
The UM-UC-3 host cell line originates from a male patient diagnosed with high-grade transitional cell carcinoma of the bladder. These epithelial cells exhibit characteristic mutations associated with bladder cancer pathogenesis and are widely utilized as a model system for bladder cancer biology, therapeutic response evaluation, and metastasis research. The adherent, tumorigenic nature of UM-UC-3 cells provides a relevant context for studying chemokine-mediated processes in bladder carcinoma.
CCL7 encodes the chemokine MCP-3 (monocyte chemotactic protein-3), a potent chemoattractant for multiple leukocyte subsets, including monocytes, eosinophils, and activated T cells. MCP-3 binds the G protein-coupled receptors CCR1, CCR2, and CCR3, which couple to G??i and trigger intracellular signaling cascades. These receptors activate PI3K-AKT and MAPK pathways, leading to phosphorylation of ERK1/2, p38 MAPK, and JNK, and subsequent activation of transcription factors NF-??B and AP-1. Upstream, CCL7 expression is induced by pro-inflammatory stimuli such as TNF, IL-1??, and IFN-??, and is regulated by STAT1 and TLR4 signaling. Downstream targets include AKT, phosphorylated ERK1/2, STAT3, MMP9, and the integrins ITGAM (CD11b) and ITGB2 (CD18), which promote cell adhesion and migration. CCL7 can form heterodimers with CCL2 and CCL5 and interacts with syndecan and glycosaminoglycans, which modulate its presentation to receptors. This signaling network orchestrates chemotaxis, tissue invasion, and immune cell recruitment.
In UM-UC-3 cells, CCL7 knockout eliminates autocrine and paracrine signaling through CCR1, CCR2, and CCR3, thereby attenuating PI3K/AKT and MAPK pathway activation. This disruption impairs chemotaxis, Matrigel invasion, and the recruitment of monocytes and other immune effector cells. Consequently, this model is instrumental for elucidating the role of CCL7 in bladder cancer progression, metastasis, and immune modulation within the tumor microenvironment.
Researchers can utilize this polyclonal knockout population to investigate CCL7-dependent tumor migration and invasion via Transwell and Matrigel assays, assess signaling changes by Western blotting for phospho-AKT (Ser473) and phospho-ERK1/2 (Thr202/Tyr204), and quantify integrin expression by flow cytometry for CD11b/CD18. RT-qPCR and ELISA enable profiling of CCL7, CCL2, and CXCL8 expression. Co-culture experiments with THP-1 monocytes and xenograft tumor studies extend these analyses. The model further supports target validation for CCR antagonists and screening for modulators of CCL7-mediated pathways. For further details, please contact Ascent Research.
