Matrigel Induces Ductal-Acinar Transdifferentiation in HSG Epithelial Cell Line

Acinar cells of exocrine glands are responsible for secretion of sufficient amount of electrolytes, water and digestive enzymes. Ductal cells, regarded to be ontogenetically preceding cell types of acini, form structural elements of the canal system of epithelial glands and modify primary secretion. Objectives: The present study was designed to examine in vitro acinar transdifferentiation of human ductal derived HSG cells, and to characterize of this process. Methods: HSG cells from human submandibular origin were cultivated in DMEM supplemented 10% FCS under standard conditions and in Matrigel matrix. Plated cells were fixed for microscopical studies to study morphological changes. The gene expression pattern of normal and differentiated HSG cells was compared by RT-PCR. DNA synthesis during the transdifferentiation process was followed by ³H-thymidine incorporation. Results: Under standard culture conditions, grown on plastic surface, HSG cells of ductal origin formed epitheloid fields and proliferated continually. Matrigel matrix containing extracellular matrix components led HSG cells to form acinar structures, and to develop dense luminar microvilli system and Golgi complex. DNA synthesis of HSG cells grown in Matrigel was 100.4%±3.8%, 36.9%±3.9%, 39.4%±2.9%, respectively, on the 1st, 2nd and 4th days after plating compared to control cells (100%) cultured on plastic surface. This clearly suggests an inhibition of proliferative activity during differentiation. Parallel to inhibition of proliferation, expression and localization of salivary amylase, antiapoptotic protein survivin and electrolyte transporters pancreatic Na⁺/HCO₃^- cotransporter 1 (pNBC1) and Na⁺-dependent chloride transporter (NKCC1) also differentially changed in HSG cells. Conclusions: The HSG cell line is a suitable in vitro model system to study cell biological mechanisms of ductal-acinar transdifferentiation of exocrine gland cells and to examine transporter molecules responsible for acinar and ductal functions.