Figure 2.

(A) We propose that the CB1 GPCRs heterodimerize with neuromedin B (NMBR) tethered to RTK in a multimeric receptor complex with matrix metalloproteinase-9 (MMP-9) and neuraminidase-1 (Neu1) in naïve (unstimulated) cancer cells. Citation: Taken in part from Bunsick et al. [52] and Haxho et al. [9]. Sialidase activity of live PANC-1 (B,C) and SW-620 (D,E) in response to AM-404, Arvanil, and Olvanil. CB1 agonists, AM-404, Arvanil, and Olvanil, significantly induce Neu-1 sialidase activity in a dose-dependent fashion compared to media control in live PANC-1 (B) and SW-620 (D). In the three cell lines, the saturation and KI concentrations for each agonist produced a more significant impact on sialidase activity compared to the latter two concentrations, which were more representative of the control. The sialidase hydrolyzed product of 4-MUNANA (4-MU) has an emission at 450 nm (blue color) when excited at 365 nm. The mean fluorescence of 50 multi-point replicates surrounding the cell’s periphery was calculated using Image J software. The mean fluorescence ± S.E.M is represented by error bars. (C,E) Different components of the signaling paradigm were inhibited using BIM-23127, an antagonist of NMBR, MMP9i, an inhibitor of MMP-9, and oseltamivir phosphate (OP), an inhibitor of Neu-1 at the indicated predetermined concentrations. The quantified data represent two to three independent experiments displaying similar results. Statistical significance, as indicated by asterisks, was calculated with ANOVA and Fisher’s uncorrected LSD multiple comparisons post hoc test at a confidence level of 95%. ns = non-significant, **** p < 0.0001, ** p < 0.01.