Posted: Wednesday, August 24, 2022
A recent study published in BMC Cancer has identified a novel mechanism that induces the activation of the Notch pathway and stimulates the proliferation of bladder cancer. According to Libo Chen, MD, of The University of South Hunan, China, and colleagues, extracellular laminin triggered the activation of the Notch pathway through integrin α6β4 and telomere repeat binding factor 3 (TRB3)/Jagged canonical Notch ligand 1 (JAG1) signaling.
“Our study demonstrated [a] novel mechanism of laminin-induced bladder cancer progression,” the study authors commented. “The development of bladder cancer stimulated by the laminin/integrin α6β4/TRB3/JAG1/Notch pathway could be inhibited by [the] Notch inhibitor SAHM1.”
The researchers used two-dimensional collagen/laminin cultures to grow cells from the human bladder cancer cell line Biu-87 and mouse bladder cancer cell line MB49; they then evaluated their ability to proliferate and migrate. To determine how laminin promoted tumor progression, the researchers examined the expression of integrin α3, α6, α7, β1, and β4 in both cell lines, as well as the expression of integrin α6 or β4 in tumor tissue from patients with non–muscle-invasive bladder cancer or muscle-invasive bladder cancer. Tumor-bearing mouse models were used to examine the effects of phosphate-buffered saline, hydroxycamptothecin (a DNA topoisomerase I inhibitor), SAHM1, or combined treatment on bladder cancer tumor growth and prognosis.
Analysis of the immunohistochemistry of 30 patients with non–muscle-invasive bladder cancer or muscle-invasive bladder cancer showed poor overall survival for patients with high expression of encoding laminin submit gamma 1. Consistent with these findings, the researchers observed that the two-dimensional laminin/collagen complex culture significantly promoted Biu-87 and MB49 cell proliferation. Further, the researchers observed that laminin activated integrin α6β4 signals to promote bladder cancer development. Lastly, the Notch inhibitor SAHM1 was shown to inhibit tumor growth in mouse models.
Disclosure: The study authors reported no conflicts of interest.