The ITGAM Knockout 786-O Polyclonal Cells product comprises a CRISPR/Cas9-edited polyclonal population derived from the 786-O human renal carcinoma cell line, engineered to disrupt the ITGAM gene encoding integrin alpha M (CD11b). This gene-edited cell pool provides a versatile loss-of-function model for investigating ITGAM-dependent biological processes. The polyclonal format offers a heterogeneous knockout background suitable for pooled functional screens and bulk assays, avoiding clonal selection artifacts.
The parental 786-O line, originally isolated from a primary clear cell renal cell carcinoma (ccRCC), is a widely utilized in vitro model for renal cancer biology. These cells display characteristic features of ccRCC, including VHL mutation-associated HIF pathway activation, and are frequently employed in studies of tumor cell adhesion, invasion, and drug response. The 786-O background thus provides a clinically relevant context for evaluating ITGAM function in renal carcinoma progression.
ITGAM encodes the integrin alpha M subunit, which heterodimerizes with integrin beta 2 (CD18) to form complement receptor 3 (Mac-1). Mac-1 serves as a receptor for complement component iC3b, ICAM-1, and other ligands, mediating cell adhesion, phagocytosis, and leukocyte migration. In the 786-O knockout pool, disruption of ITGAM abolishes Mac-1 surface expression, impairing ligand binding. Downstream signaling through non-receptor tyrosine kinases such as SYK and FAK (PTK2) is attenuated, leading to reduced activation of PI3K/AKT and MAPK/ERK pathways. ITGAM expression is known to be regulated by transcription factors PU.1 (SPI1) and NF-??B in response to inflammatory stimuli like TNF-?? and LPS. The integrin also interacts with cytoskeletal adaptors talin and kindlin, linking extracellular adhesion to intracellular actin dynamics.
In the 786-O ccRCC context, ITGAM knockout addresses the emerging role of integrin-mediated adhesion in cancer cell dissemination. Although Mac-1 is classically associated with leukocytes, ectopic or low-level expression of ITGAM has been reported in some non-hematopoietic tumors. By eliminating ITGAM, researchers can dissect contributions of this integrin to renal carcinoma cell attachment, spreading, and transendothelial migration. The model is particularly useful for studying crosstalk between complement and tumor cell motility, as well as for validating integrin antagonists in a cancer background. Loss of ITGAM also allows investigation of compensatory adhesion mechanisms and rewiring of downstream signaling networks in the absence of Mac-1.
Researchers can employ the ITGAM Knockout 786-O Polyclonal Cells in a variety of functional assays, including flow cytometric confirmation of CD11b loss, adhesion assays on ICAM-1- or iC3b-coated surfaces, and Boyden chamber or transwell migration experiments. Co-immunoprecipitation with ITGB2 confirms disruption of the ??M??2 complex, while immunofluorescence reveals altered integrin localization. The cells further facilitate drug target validation for anti-integrin therapies and mechanistic studies of immune?Ccancer cell interactions. For ordering information or technical assistance, please contact Ascent Research.
