Journal of Carcinogenesis & Mutagenesis

Abstract

Secreted Protein Acidic and Rich in Cysteine (SPARC) in Cancer

Neveen Said and Dan Theodorescu

The local tissue microenvironment “niche” is composed of cellular and non-cellular components and plays an important role in regulating cell behaviour, during embryogenesis, and in physiologic and pathologic contexts including cancer. The cellular component is formed of specialized cell types endowed for the biological functions of the organ and tissues. The non-cellular component of the niche comprises the extracellular matrix (ECM) which functions not only as a scaffold for the cellular component maintaining tissue morphology, but dynamically influences fundamental aspects of cell behaviour. Matricellular proteins are a group of extracellular matrix (ECM) molecules that are not components of the structural scaffold of the ECM but serve as cell regulators and modulators of cellular behaviour and signaling. Secreted Protein Acidic and Rich in Cysteine (SPARC) is one of the matricellular proteins and is implicated in myriad physiological and pathological conditions characterized by extensive remodelling and plasticity. The role of SPARC in cancer is being increasingly recognized as it plays multi-faceted contextual roles depending on the cancer type, cell of origin and the surrounding milieu. The role of SPARC in the multistep cascades of carcinogenesis, cancer progression and metastasis has been studied retrospectively in human tumors, preclinical models using cell lines and models of oncogene-driven and carcinogen-induced cancers. Below we review several of these tumor types where SPARC biology has been evaluated.