Periostin: A Matricellular Protein With Multiple Functions in Cancer Development and Progression

Tumor microenvironment is considered nowadays as one of the main players in cancer development and progression. Tumor microenvironment is highly complex and consists of non-tumor cells (i.e., cancer-associated fibroblast, endothelial cells, or infiltrating leukocytes) and a large list of extracellular matrix proteins and soluble factors. The way that microenvironment components interact among them and with the tumor cells is very complex and only partially understood. However, it is now clear that these interactions govern and modulate many of the cancer hallmarks such as cell proliferation, the resistance to death, the differentiation state of tumor cells, their ability to migrate and metastasize, and the immune response against tumor cells. One of the microenvironment components that have emerged in the last years with strength is a heterogeneous group of multifaceted proteins grouped under the name of matricellular proteins. Matricellular proteins are a family of non-structural matrix proteins that regulate a variety of biological processes in normal and pathological situations. Many components of this family such as periostin (POSTN), osteopontin (SPP1), or the CNN family of proteins have been shown to regulate key aspect of tumor biology, including proliferation, invasion, matrix remodeling, and dissemination to pre-metastatic niches in distant organs. Matricellular proteins can be produced by tumor cells themselves or by tumor-associated cells, and their synthesis can be affected by intrinsic and/or extrinsic tumor cell factors. In this review, we will focus on the role of POSTN in the development and progression of cancer. We will describe their functions in normal tissues and the mechanisms involved in their regulation. We will analyze the tumors in which their expression is altered and their usefulness as a biomarker of tumor progression. Finally, we will speculate about future directions for research and therapeutic approaches targeting POSTN.We sincerely apologize to all colleagues whose work has not been cited adequately in this review, either due to space limitations or unintentional omission. LG-G and JA are supported by Asociación Pablo Ugarte, ASION-La Hucha de Tomás, Fundación “Sonrisa de Alex,” and Instituto de Salud Carlos III (PI16CIII/00026). Some elements used to draw image 1 are attributed to Smart Servier Medical Art (smart.servier.com), which are licensed under a Creative Commons Attribution 3.0 Unported License.S