Diverse biological functions of the SPARC family of proteins

Abstract

The SPARC family of proteins represents a diverse group of proteins that modulate cell interaction with the extracellular milieu. The eight members of the SPARC protein family are modular in nature. Each shares a follistatin-like domain and an extracellular calcium binding E–F hand motif. In addition, each family member is secreted into the extracellular space. Some of the shared activities of this family include, regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways. Recently, several SPARC family members have been implicated in human disease pathogenesis. This review discusses recent advances in the understanding of the functional roles of the SPARC family of proteins in development and disease.

Tumour-derived SPARC drives vascular permeability and extravasation through endothelial VCAM1 signalling to promote metastasis

“…In melanoma, we and others have previously identified an autocrine role for SPARC in regulating invasiveness, epithelial-mesenchymal-like transition and melanoma survival [14][15][16]42 . Although SPARC expression has been clearly linked to cancer progression through cell-autonomous and non-autonomous actions in cell invasion and survival 20,43,44 , its function as a paracrine factor has remained poorly characterized. Paracrine functions attributed so far to SPARC in melanoma were related to inhibition of polymorphonuclear leukocyte recruitment 43 , and inhibition of proliferation and migration capacities of endothelial cells in vitro 45 .…”

“…Other proteins differentially expressed in 1205Lu CM versus 501Mel included factors involved in additional important tumour cell functionalities such as angiogenesis (NRP1), fibrinolysis (PAI1, GDN, UPAR) or associated with extracellular microvesicles and exosomes (HS90B, RAB7A). The discovery that SPARC, a matricellular protein involved in tumour cell invasion and survival 20 , and endothelial barrier function 21 , was 10-fold more abundant in metastatic melanoma cell CM as compared with CM from a poorly metastatic cell prompted us to investigate whether SPARC contributes to paracrine induction of vascular permeability by melanoma cellderived CM. We, therefore, engaged different approaches to manipulate SPARC expression and function.…”

Matricellular protein SPARCL1 regulates tumor microenvironment–dependent endothelial cell heterogeneity in colorectal carcinoma

“…SPARCL1 is described as an antiadhesive protein (38) that exerts antitumorigenic activity specifically in CRC if recombinantly expressed in or added as a purified protein to RKO or SW620 cell lines (24,37). As yet in CRC tissues, SPARCL1 expression has been detected in CRC tissues, but conflicting results exist with respect to its presence in tumor cells and/or ECs, and, as such, its association with prognosis is a subject of controversy (24,39).…”

Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation

“…Although in many cases the effects of matricellular proteins on cell adhesion relate to integrin binding, the effects of TSP-2 on cell adhesion are thought to be mediated by MMP regulation, though altered matrix and growth factor interactions may also play a role (10). Many matricellular proteins in fact regulate MMPs, for example, the SPOCK family of proteins exhibit a complex regulation of MMP activity (23) and SPARC can upregulate expression of multiple MMPs in cancer cells (24). Through MMP regulation matricellular proteins can further influence not just cell adhesion and migration but also cell growth, as MMPs can activate and release growth factors such as VEGF and TGFβ (25).…”