Integrins are a large family of transmembrane molecules that mediate cell contact with the extracellular environment, especially the extracellular matrix. Integrin-mediated contact with the basement membrane underlying glandular epithelial cells, such as pancreatic acini, determines cellular polarity required for appropriate exocrine function. Growing evidence from in vivo and in vitro studies highlights the requirement of β1 integrin function in stem cells and in three-dimensional tumor biology, where the β1 integrin modulates cellular differentiation and contributes to the malignant behavior of cancer cells.

I tested hypothesis that β1 integrin ablation in the pancreas would eliminate the ability of acinar cells to maintain contact with the basement membrane, potentially compromising their function in both normal and pathological situations.

In order to address these questions and understand the fate of acinar cells lacking BM contact, a pancreas-specific knockout of β1 integrin was developed. This allowed us to follow completely the biology of acinar cells, from development to adulthood, in normal condition and in the context of experimental pancreatitis.

In my studies, I found that β1 integrin was not required for the initial establishment of acinar cell polarity, but was necessary for the maintenance of acinar homeostasis. I showed that β1 integrin is involved in directional secretion, and this is a critical element for the maintenance of acinar cell integrity.

Finally, I suggest the possibility that the contribution of β1 integrin might be related to its signaling function, rather than to the role of physical cell-cell and cell-BM link. Accordingly, identifying the signaling defect that lead β1 null mice to irreversible degeneration, could lead the way for the development of therapy of acute and chronic pancreatitis.