Osteopontin in pancreatic cancer: A systematic review.

The present study analyzed the available literature on osteopontin in pancreatic cancers. Before the cut-off date, PubMed listed 105 pertinent references, plus 39 results covering osteopontin in non-cancerous conditions of the pancreas. The molecule fulfills physiologic roles in pancreatic development and function, including islet survival and protection from hyperglycemia. Osteopontin has been found upregulated in cancers of the pancreas and may serve as a biomarker for transformation, progression or survival prospects, particularly in conjunction with other molecular indicators. It has been reliably corroborated as a blood biomarker for these malignancies. In particular, the measurement of the cancer-specific osteopontin splice variants OPN-b and OPN-c achieves upgraded diagnosis. Animal and cellular models have elucidated the functions of osteopontin in support of the metastasis, tropism and stemness of the cancer cells, as well as roles in angiogenesis and chemoresistance. As the full-length form of osteopontin, OPN-a, serves as an inducer cytokine for cellular immunity, it has been characterized by several studies as a regulator in pancreatic tumor immunology, particularly in macrophages. Osteopontin induction and biologic effects are associated with various premalignant and predisposing conditions, including intraductal papillary mucinous neoplasms, smoking, pancreatitis and kidney disease. In diabetes and obesity, the molecule plays complex roles that may either attenuate or promote disease progression. While osteopontin has emerged as a key physiological regulator of pancreatic functions, its aberrant expression and splicing in cancers of the pancreas supports tumor progression and may serve early detection as well as prognostication. The splice variants have potential to become therapeutic targets in anti-metastasis regimens.