Progranulin/GP88, A Complex and Multifaceted Player of Tumor Growth by Direct Action and via the Tumor Microenvironment.

Investigation of the role of progranulin/GP88 on the proliferation and survival of a wide variety of cells has been steadily increasing. Several human diseases stem from progranulin dysregulation either through its overexpression in cancer or its absence as in the case of null mutations in some form of frontotemporal dementia. The present review focuses on the role of progranulin/GP88 in cancer development, progression, and drug resistance. Various aspects of progranulin identification, biology, and signaling pathways will be described. Information will be provided about its direct role as an autocrine growth and survival factor and its paracrine effect as a systemic factor as well as via interaction with extracellular matrix proteins and with components of the tumor microenvironment to influence drug resistance, migration, angiogenesis, inflammation, and immune modulation. This chapter will also describe studies examining progranulin/GP88 tumor tissue expression as well as circulating level as a prognostic factor for several cancers. Due to the wealth of publications in progranulin, this review does not attempt to be exhaustive but rather provide a thread to lead the readers toward more in-depth exploration of this fascinating and unique protein.