The GPNMB Knockout UM-UC-3 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population targeting the GPNMB gene in the UM-UC-3 human urothelial carcinoma cell line. This loss-of-function model enables investigation of glycoprotein nonmetastatic melanoma protein B (GPNMB) biological functions. The polyclonal format provides a heterogeneous edited cell pool, reflecting cancer genetic variability and facilitating robust analyses free of clonal selection artifacts.
UM-UC-3 cells were established from a male patient with invasive bladder transitional cell carcinoma. This line is widely used as a model for muscle-invasive bladder cancer, exhibiting key characteristics such as anchorage-independent growth, high tumorigenicity, and metastatic potential. Its aggressive phenotype makes it an ideal host for CRISPR-based gene disruption to study molecular mechanisms driving urothelial carcinoma progression.
GPNMB is a transmembrane glycoprotein that promotes cell adhesion, migration, and tumor invasion. Transcriptionally regulated by MITF and activated by TGF-beta, IL-6, and hypoxia, GPNMB interacts with integrin alphaVbeta3, heparan sulfate proteoglycans, CD44, and EGFR. These interactions activate FAK and downstream ERK1/2 and AKT pathways, while also modulating p38 MAPK. Pathway activation leads to increased MMP-9 and VEGF expression, enhancing extracellular matrix degradation and angiogenesis. GPNMB also participates in osteoblast differentiation and lysosomal function, linking it to bone remodeling and lysosomal storage disorders.
In the UM-UC-3 context, GPNMB knockout disrupts these oncogenic signals, resulting in impaired proliferation, migration, and invasion. Loss of GPNMB reduces integrin and growth factor receptor crosstalk, attenuating ERK1/2 and AKT phosphorylation and decreasing MMP and VEGF output. This polyclonal knockout model recapitulates a GPNMB-deficient state in aggressive bladder cancer, enabling mechanistic studies and therapeutic target validation.
Applications include functional studies of bladder cancer metastasis, tumor-stroma interaction analysis, and drug screening for GPNMB inhibitors. Researchers can use western blotting and RT-qPCR for knockout confirmation, MTT and wound healing assays for proliferation and migration, and Transwell and Matrigel invasion assays for invasive capacity. Phospho-kinase arrays reveal pathway changes, while xenograft models assess in vivo tumor growth and metastasis. For further details, contact Ascent Research.
