A novel 4D cell culture mimicking stomach peristalsis altered gastric cancer spheroids growth and malignance

Abstract

Abstract In vitro cancer models that can largely mimic the in vivo microenvironment are crucial for conducting more accurate research. Models of three-dimensional (3D) culture that can mimic some aspects of cancer microenvironment or cancer biopsies that can adequately represent tumor heterogeneity are intensely used currently. Those models still lack the dynamic stress stimuli in gastric carcinoma exposed to stomach peristalsis in vivo. This study leveraged a lab-developed four-dimensional (4D) culture model by a magnetic responsive alginate-based hydrogel to rotating magnets that can mimic stress stimuli in gastric cancer (GC). We used the 4D model to culture human GC cell line AGS and SGC7901, cells at the primary and metastasis stage. We revealed the 4D model altered the cancer cell growth kinetics mechanistically by altering PCNA and p53 expression compared to the 3D culture that lacks stress stimuli. We found the 4D model altered the cancer spheroids stemness as evidenced by enhanced cancer stem cells (CD44) marker expression in AGS spheroids but the expression was dampened in SGC7901 cells. We examined the multi-drug resistance (MDR1) marker expression and found the 4D model dampened the MDR1 expression in SGC7901 cell spheroids, but not in spheroids of AGS cells. Such a model provides the stomach peristalsis mimic and is promising for conducting basic or translational GC-associated research, drug screening, and culturing patient gastric biopsies to tailor the therapeutic strategies in precision medicine.