The CCL7 Knockout 786-O Polyclonal Cells constitute a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 786-O human renal cell adenocarcinoma line, in which the gene encoding chemokine CCL7 has been disrupted. This polyclonal format comprises a heterogeneous pool of edited cells harboring distinct loss-of-function mutations, providing robust ablation of target gene expression across the bulk culture. By avoiding single-cell cloning, the population minimizes clonal selection artifacts and better represents functional heterogeneity. The product is supplied as an assay-ready resource, validated for gene disruption and negative for mycoplasma contamination.
The host 786-O cell line is a widely utilized model of clear cell renal cell carcinoma, originally derived from a primary tumor bearing a VHL-inactivating mutation. This VHL deficiency leads to constitutive stabilization of HIF transcription factors, driving a pseudohypoxic state that upregulates genes involved in angiogenesis, metabolism, and immune modulation. The epithelial origin and genetic tractability of 786-O cells make them particularly suitable for studying tumor-intrinsic signaling and paracrine communication within the renal cancer microenvironment.
CCL7, also termed MCP-3, is a secreted chemokine that orchestrates leukocyte trafficking by binding to CCR1, CCR2, CCR3, and CCR5 receptors expressed on monocytes, dendritic cells, eosinophils, basophils, and activated T cells. Ligand-receptor engagement triggers heterotrimeric G-protein activation, leading to JAK2-dependent STAT3 phosphorylation, ERK1/2 kinase activation, and AKT signaling, which collectively promote directed cell migration through calcium mobilization and cytoskeletal remodeling. Transcriptionally, CCL7 is under the control of pro-inflammatory mediators: TNF-??, IL-1??, and IFN-?? act via NF-??B and AP-1 to induce its expression, while TLR ligands further amplify this response. Consequently, CCL7 integrates signals from the chemokine, cytokine-cytokine receptor, JAK-STAT, NF-??B, MAPK, and PI3K-Akt pathways.
In the context of VHL-mutant 786-O cells, knockout of CCL7 eliminates a key autocrine and paracrine chemoattractant signal, potentially impairing the recruitment of CCR-expressing immune cells into the tumor milieu. This disruption allows dissection of CCL7-dependent mechanisms in tumor progression, metastasis, and the establishment of an immunosuppressive or pro-inflammatory niche. Moreover, because HIF-driven transcriptional programs intersect with chemokine regulation, the model enables exploration of how renal carcinoma cells shape their microenvironment under pseudohypoxic conditions in the absence of CCL7.
Researchers can employ this knockout model in chemotaxis, migration, and invasion assays to quantify CCL7-mediated cell motility, and in cytokine arrays to profile altered secretory profiles. The cells are suited for xenograft tumor growth studies to assess the impact of CCL7 loss on tumorigenesis and immune infiltration in vivo. Additionally, combining the polyclonal knockout cells with transcriptomic or proteomic approaches facilitates the identification of downstream targets and compensatory pathways. For further information, please contact Ascent Research.
