Serglycin has been initially characterized as an intracellular proteoglycan expressed by hematopoietic cells. All inflammatory cells highly synthesize serglycin and store it in granules, where it interacts with numerous inflammatory mediators, such as proteases, chemokines, cytokines, and growth factors. Serglycin is implicated in their storage into the granules and their protection since they are secreted as complexes and delivered to their targets after secretion. During the last decade, numerous studies have demonstrated that serglycin is also synthesized by various non-hematopoietic cell types. It has been shown that serglycin is highly expressed by tumor cells and promotes their aggressive phenotype and confers resistance against drugs and complement system attack. Apart from its direct beneficial role to tumor cells, serglycin may promote the inflammatory process in the tumor cell microenvironment thus enhancing tumor development. In the present review, we discuss the role of serglycin in inflammation and tumor progression.

Serglycin is a proteoglycan expressed by some malignant cells. It promotes metastasis and protects some tumor cells from complement system attack. In the present study, we show for the first time the in situ expression of serglycin by breast cancer cells by immunohistochemistry in patients’ material. Moreover, we demonstrate high expression and constitutive secretion of serglycin in the aggressive MDA-MB-231 breast cancer cell line. Serglycin exhibited a strong cytoplasmic staining in these cells, observable at the cell periphery in a thread of filaments near the cell membrane, but also in filopodia-like structures. Serglycin was purified from conditioned medium of MDA-MB-231 cells, and represented the major proteoglycan secreted by these cells, having a molecular size of ∼250 kDa and carrying chondroitin sulfate side chains, mainly composed of 4-sulfated (∼87%), 6-sulfated (∼10%) and non-sulfated (∼3%) disaccharides. Purified serglycin inhibited early steps of both the classical and the lectin pathways of complement by binding to C1q and mannose-binding lectin. Stable expression of serglycin in less aggressive MCF-7 breast cancer cells induced their proliferation, anchorage-independent growth, migration and invasion. Interestingly, over-expression of serglycin lacking the glycosaminoglycan attachment sites failed to promote these cellular functions, suggesting that glycanation of serglycin is a pre-requisite for its oncogenic properties. Our findings suggest that serglycin promotes a more aggressive cancer cell phenotype and may protect breast cancer cells from complement attack supporting their survival and expansion.

The pathogenesis of colorectal carcinoma (CRC) is a complex process that involves the recruitment of both genetic and epigenetic mechanisms. Recent studies underline the cardinal role of small, noncoding RNA molecules, called microRNAs (miRs), in the pathobiology of numerous physiological and pathological processes, including oncogenesis. MiR biogenesis and maturation is mainly regulated by the nuclear ribonuclease Drosha and the cytoplasmic ribonucleases Dicer and Ago2. In the present study, we investigated the expression and distribution of these molecules in three colon cancer cell lines and in human CRC samples. Drosha, Dicer, and Ago2 mRNA and protein expression was assessed with real-time PCR, western blotting, and immunofluorescence. Our experiments showed that Drosha, Dicer, and Ago2 were expressed in all the cell lines and in the majority of the CRC samples examined. The mRNA levels of Dicer were significantly augmented in stage III compared to stage II tumors. Our results suggest that Drosha, Dicer, and Ago2 are possibly implicated in CRC pathobiology and that Dicer might have a role in the progression of these tumors to advanced stages.

Our results point at a role of Drosha, Dicer and Ago2 in the development of NSCLC and suggest that Dicer may be implicated in the progression of these tumors to advanced stages.