The CD38 Knockout 786-O Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population featuring targeted disruption of the CD38 gene in the human 786-O renal adenocarcinoma cell line. This polyclonal format provides a heterogeneous pool of edited cells, enabling robust assessment of CD38-dependent phenotypes while minimizing clonal selection biases. The model serves as a critical tool for interrogating CD38-mediated NAD+ metabolism and calcium signaling pathways in a cancer context.
The 786-O host cell line is an epithelial line isolated from a primary clear cell renal cell carcinoma, extensively employed as a model for renal cancer biology. Characterized by VHL tumor suppressor inactivation, 786-O cells exhibit dysregulated hypoxia-inducible factor signaling and metabolic reprogramming, making them particularly suitable for investigating CD38’s role in calcium homeostasis, proliferation, and immune modulation within the tumor microenvironment.
CD38 encodes a multifunctional type II transmembrane glycoprotein that functions both as an ectoenzyme and a receptor. Its enzymatic activity generates the potent calcium-mobilizing second messengers cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) from NAD+. Upstream, CD38 expression is induced by interferon-gamma, TNF-alpha, retinoic acid, and vitamin D, and its receptor function involves interaction with CD31 (PECAM-1) and downstream adaptors such as SLP-76 and Lck. These messengers then trigger calcium release through ryanodine receptors (RyR) and TPC2 channels, respectively, leading to activation of ERK and AKT kinases. Through these mechanisms, CD38 integrates calcium signaling, cell adhesion, and immune cell effector functions.
In the 786-O adenocarcinoma background, CD38 knockout ablates cADPR and NAADP production, thereby impairing intracellular calcium mobilization. This disruption is predicted to attenuate calcium-dependent signaling cascades, potentially reducing cell proliferation, adhesion, and survival. Moreover, loss of CD38 may alter the immunomodulatory properties of these tumor cells, providing a valuable model to dissect CD38??s contributions to immune evasion and tumor progression in renal cell carcinoma.
This product is designed for a broad range of functional studies, including quantitative calcium flux assays using fluorescent indicators, cell proliferation and adhesion assays, and metabolic analysis of NAD+ and its derivatives by mass spectrometry. Molecular validation can be performed via western blotting for CD38 and downstream effectors, while RT-qPCR enables transcriptional profiling. Flow cytometric assessment of surface CD38 confirms gene disruption. These cells are also ideal for drug screening targeting CD38-related pathways and for co-culture experiments analyzing tumor-immune cell interactions. For further information, please contact Ascent Research.
