TABLE 2.

Role of SDCs in other diseases

SDC	Pathologies	Function	References
SDC-1	T1DM/ T2DM DN	In diabetic patients with DN, serum levels of SDC-1 as well as surface expression of neutrophils was higher (only in T2DM).	Kolseth et al. (2017), Pletinck et al. (2012), Wang et al. (2012)
	Diabetic enteropathy	Interaction between SDC-1 and heparanase is important for intestinal epithelial barrier. Shedding of SDC-1 and high heparanase activity correlates with increased intestinal permeability along with activation of p38 MAPK pathway.	Bode et al. (2008), Qing et al. (2015)
	HIV	Tat engages SDC-1, chemokine receptors, and intergrins to promote pathogenesis of AID-related lymphomas.	Urbinati et al. (2016)
	Cancer	High SDC-1 expression in many solid cancers including head and neck, ovarian, breast, prostate, and colon carcinomas is associated with cancer initiation, proliferation, and survival, since SDC-1 can bind to many growth factors and works as a cofactor to enhance downstream pathways including STAT3, Notch, EGFR, and Wnt-1 signaling pathways. SDC-1 can also function inside the cells by co-localizing with mitotic spindle during mitosis and modulating transcription factors and other nuclear protein to regulate cell division. However, lower levels have also been associated with poor prognosis in many cancer including mesothelioma, lung carcinoma, breast cancer, gastric carcinoma, and myeloma. In these cases, higher SDC-1 level facilitated adhesion to ECM and inhibited invasion and metastasis. Increased shedding of SDC-1 by heparanase and other sheddases promoted more aggressive tumor phenotype as observed in myeloma and gallbladder carcinoma. In addition to sheddases, miR-10b that downregulates SDC-1 expression has been shown to be overexpressed in breast cancer and overexpression of miR-10b increased invasiveness.	Alexander et al. (2000), Anttonen et al. (2001), Baba et al. (2006), Brockstedt et al. (2002), Cheng et al. (2001), Chu et al. (2008), Hannafon et al. (2011), Hassan et al. (2013), Ibrahim et al. (2012, 2017), Jin et al. (2017), Kumar-Singh et al. (1998), Liu et al. (2003), Maeda et al. (2004), Maeda et al. (2006), Mikami et al. (2001), Nguyen et al. (2013), Nilsson et al. (2010), Ramani et al. (2013), Shimada et al. (2009, 2013), Teng et al. (2012), Wei et al. (2015)
SDC-2	T2DM	In the brain, SDC-3 binds to N-terminal domain of AgRP, and this interaction promotes C-terminal domain of AgRP to competitively bind to MC4-R and thus enhance orexigenic stimulus.	Reizes et al. (2003, 2008)
	Cancer	Silencing SDC-2 in breast cancer significantly reduced metastasis.	Lim et al. (2015)
SDC-3	HIV	MDCCs capture and present HIV antigens to cytolytic CD8+ T cells through gpl20 and SDC-3 interaction.	de Witte et al. (2007)
SDC-4	Cancer	In breast cancer, SDC-4 expression is associated with estrogen and progesterone receptor positive cells and may function in cell adhesion and spreading.	Baba et al. (2006), Beauvais and Rapraeger, (2003)