The ITGAM Knockout 769-P Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population derived from the 769-P human clear cell renal cell carcinoma line. This product provides a heterogeneous pool of cells carrying targeted disruptions in the ITGAM gene, leading to loss of integrin alpha-M (CD11b) expression. The polyclonal format avoids clonal bias and supplies a robust loss-of-function model. The knockout is achieved through CRISPR/Cas9-mediated gene disruption, enabling functional studies of CD11b-dependent signaling.
The 769-P cell line was established from a primary clear cell adenocarcinoma of the kidney in a 63-year-old male. It exhibits adherent epithelial morphology and retains key molecular features of clear cell renal cell carcinoma (ccRCC). This host provides a clinically relevant model for investigating tumor biology, including adhesion, migration, and interactions with the immune microenvironment. Its use in creating the ITGAM knockout enables dissection of integrin ??M functions specifically within a carcinoma context, complementing studies in immune cells.
ITGAM encodes integrin ??M, which pairs with CD18 to form complement receptor 3 (CR3). CR3 binds ligands such as iC3b, ICAM-1, and fibrinogen, mediating leukocyte adhesion, phagocytosis, and chemotaxis. Inside-out activation involves talin and kindlin-3, while downstream signaling proceeds through Src, FAK, Syk, PI3K/Akt, and MAPK pathways (ERK, p38). ITGAM expression is regulated by transcription factors PU.1 and C/EBP?? and cytokines like TNF-?? and TGF-??. CRISPR-mediated ITGAM knockout abrogates CD11b surface expression, thereby disrupting CR3-mediated functions and downstream signaling cascades.
In 769-P renal carcinoma cells, ITGAM knockout permits examination of CD11b??s role in tumor-ECM adhesion, cell motility, and potential immunomodulatory functions. This model aids investigation of how integrin ??M influences ccRCC metastasis and immune evasion. Given CR3??s involvement in inflammatory and autoimmune conditions??including systemic lupus erythematosus and glomerulonephritis??these cells also provide a platform for studying ITGAM-related pathobiology in kidney-derived cancers. The knockout context reveals cancer cell-intrinsic contributions of CD11b that may differ from its classical leukocyte roles.
Applications include Western blotting and flow cytometry for CD11b detection, adhesion and migration assays to assess integrin function, and phagocytosis assays to probe CR3-mediated uptake. Co-immunoprecipitation can map CD11b interactions with CD18 and adaptors. These polyclonal knockout cells are also valuable for drug target validation targeting integrin pathways. The product supports rigorous and reproducible research into ITGAM biology. For further information, please contact Ascent Research.
