Tumor growth is essentially the result of an evolving cross-talk between malignant and surrounding stromal cells (fibroblasts, endothelial cells and inflammatory cells). This heterogeneous mass of extracellular matrix and intermingled cells interact through cell-cell and cell-matrix contacts. Malignant cells also secrete soluble proteins that reach neighbor stromal cells, forcing them to provide the soil on which they will grow and metastasize. Different studies including expression array analysis identified the matricellular protein SPARC as a marker of poor prognosis in different cancer types. Further evidence demonstrated that high SPARC levels are often associated with the most aggressive and highly metastatic tumors. Here we describe the most recent evidence that links SPARC with human cancer progression, the controversy regarding its role in certain human cancers and the physiological processes in which SPARC is involved: epithelial-mesenchymal transition, immune surveillance and angiogenesis. Its relevance as a potential target in cancer therapy is also discussed.

The expression of secreted protein acidic and rich in cysteine (SPARC) has been associated with the malignant progression of different types of human cancer. SPARC was associated with tumor cell capacity to migrate and invade, although its precise role in tumor progression is still elusive. In the present study, we show that SPARC produced by melanoma cells modulates the antitumor activity of polymorphonuclear leukocytes (PMN). Administration to nude mice of human melanoma cells in which SPARC expression was transiently or stably knocked down by antisense RNA (SPARC-sup cells) promoted PMN recruitment and obliterated tumor growth even when SPARC-sup cells accounted for only 10% of injected malignant cells. In addition, SPARC-sup cells stimulated the in vitro migration and triggered the antimelanoma cytotoxic capacity of human PMN, an effect that was reverted in the presence of SPARC purified from melanoma cells or by reexpressing SPARC in SPARC-sup cells. Leukotrienes, interleukin 8, and growth-related oncogene, in combination with Fas ligand and interleukin 1, mediated SPARC effects. These data indicate that SPARC plays an essential role in tumor evasion from immune surveillance through the inhibition of the antitumor PMN activity. (Cancer Res 2005; 65(12): 5123-32)