E destruction [349]. Recently, increased expression of serglycin has been confirmed in nasopharyngeal and hepatocellular carcinoma. The elevated levels of serglycin in individuals is correlated with unfavorable Complement Component 2 Proteins Formulation prognosis for all round survival and recurrence in nasopharyngeal cancer and for disease cost-free and distant metastasis no cost survival in HCC [350, 351]. Serglycin secreted from metastatic nasopharyngeal carcinoma cells promotes EMT, motility, invasion, and metastasis [351]. Non-glycanated core protein of serglycin fails to induce cancer cell motility suggesting the involvement of GAG chains in tumor advertising properties of serglycin.Author Manuscript Author Manuscript Author Manuscript Author ManuscriptBiochim Biophys Acta. Author manuscript; available in PMC 2016 April 01.Theocharis et al.PageSerglycin is extremely expressed in breast cancer tissues and cell lines [33]. The mRNA levels of serglycin are markedly up-regulated in aggressive breast cancer cells clustered into Basal B subgroup, which exhibit an EMT gene signature and resemble breast cancer stem cells getting CD44highCD24low [33]. Basal-like breast cancers are correlated with elevated danger of metastatic spread and poor patient prognosis. In contrast, serglycin is expressed in low levels in much less aggressive subtypes of breast cancer cells [33]. Biochemical characterization of proteoglycans secreted by aggressive MDA-MB-231 breast cancer cells demonstrated that serglycin bearing CS chains could be the main secreted proteoglycan and it is actually abundantly present within the cytoplasm and cell membrane displaying each filamentous and granular distribution [33]. Serglycin promotes breast cancer cell anchorage-independent development, migration and invasion when it is over-expressed in minimally invasive MCF-7 breast cancer cells. Interestingly, over-expression of a mutant type of serglycin lacking GAG attachment web-sites fails to induce breast cancer cell aggressiveness demonstrating that precise structure of CS-4S present on serglycin is significant for its functions in breast cancer [33]. CHST11 gene that specifically mediates 4-O sulfation of CS is very expressed in MDA-MB-231 breast cancer cells promoting their binding to P-selectin by means of CS-4S chains and facilitating the formation of metastasis [352]. It is also of wonderful value that CS-4 chains regulates the functional properties of proteolytic enzymes such as cathepsins, which are involved in ECM degradation and tumor metastases [8]. Serglycin also regulates immune system by means of its capability to inhibit complement program activity. Serglycin isolated from myeloma and breast cancer cells inhibits the classical as well as the lectin pathways of complement program by way of direct binding to C1q and MBL, respectively, and protects tumor cells from complement program attack [33, 353]. Only these CS-4S chains using a high proportion of 4-sulfated disaccharides interact efficiently with complement proteins [353]. CS-E and within a reduced extent heparin compete with CS-4 chains of serglycin for binding to C1q, whereas only CS-E competes for binding to MBL. Binding of serglycin to C1q or/and C1 inhibits the cleavage of C4 within the classical pathway. Within the lectin pathway, binding of serglycin to MBL either competes out MBL-associated proteases (MASPs) in the stalk area of MBL or sterically hinders cleavage of C2 and C4 by MASPs [353]. The inhibition of complement is a great IL-21R Proteins MedChemExpress limitation for the duration of immunotherapy against numerous sorts of cancer. These findings recommend a function for serglycin.