Small Leucine‐Rich Proteoglycans in Cancer: Three Decades of Discovery

ABSTRACT

Small leucine‐rich proteoglycans (SLRPs) are a well‐known family of extracellular matrix (ECM) molecules. They consist of five classes with 18 different protein cores originally recognized as having a physically supportive component to the extracellular structure and tissue integrity. There has been a significant conceptual shift from the original paradigm as mere contributors to ECM structure to the current concept of bioactive signaling molecules. Over the past three decades, SLRPs have evolved into critical modulators of signaling events in cells by contributing to the regulation of receptor activity and intercellular communication. They also affect key biological processes such as tissue remodeling, inflammation, and autophagy. Through interactions with receptor tyrosine kinases, integrins, and growth factors they regulate signaling pathways involved in cell proliferation, survival, and migration. These biological interactions allow for the regulation of cellular function and microenvironment homeostasis in a context dependent manner. In this review, we will comprehensively assess all 18 SLRPs in their relation to cancer biology and analyze how they contribute to the initiation and development of tumors and the regulation of stroma. Abnormal SLRP signaling will disturb the ECM cellular interactions and responses, which may result in oncogenic progression.