Expression and Roles of Lumican, a Small Leucine-rich Proteoglycan, in Gastrointestinal and Other Cancers

Abstract

Lumican is a member of classⅡof the small leucine-rich proteoglycan family, and it was first reported as a keratin sulfatecontaining proteoglycan in the cornea. Lumican plays an important role in collagen fibrillogenesis in cornea and other various human tissues. Recently, a number of reports have shown that lumican is expressed in several types of malignant tumors including gastrointestinal cancers; however, the roles of lumican in the tumors are quite variable. In neuroendocrine tumors of the colon, for example, lumican expression in the cytoplasm is negatively correlated with tumor malignancy grade. Increased expression of lumican in malignant melanoma and osteosarcoma inhibits their aggressive growth. In contrast, the localization of lumican in the stromal tissue correlates with advanced cancer stage and retroperitoneal and duodenal invasion and residual tumor presence of pancreatic cancer, and increased secretion of lumican in the extracellular space induces growth of the cancer. Lumican in colorectal cancer has tended to correlate with the spread of lymph node metastasis and the depth of tumor invasion. The reason for these opposing effects of lumican in different cancers is not well understood, but different glycosylation patterns of lumican or receptors and in the cell signaling pathways involved may play pivotal roles in its cancer cell behaviors. This review article summarizes the expression and roles of lumican in malignant tumors, including gastrointestinal cancers, and discusses the possibility of using lumican as a diagnostic marker and novel therapeutic target for cancers.