Abstract
In the present pilot study, we examined the presence of serglycin in lung, breast, prostate, and colon cancer and evaluated its expression in cell lines and tissues. We found that serglycin was expressed and constitutively secreted in culture medium in high levels in more aggressive cancer cells. It is worth noticing that aggressive cancer cells that harbor KRAS or EGFR mutations secreted serglycin constitutively in elevated levels. Furthermore, we detected the transcription of an alternative splice variant of serglycin lacking exon 2 in specific cell lines. In a limited number of tissue samples analyzed, serglycin was detected in normal epithelium but was also expressed in higher levels in advanced grade tumors as shown by immunohistochemistry. Serglycin staining was diffuse, granular, and mainly cytoplasmic. In some cancer cells serglycin also exhibited membrane and/or nuclear immunolocalization. Interestingly, the stromal cells of the reactive tumor stroma were positive for serglycin, suggesting an enhanced biosynthesis for this proteoglycan in activated tumor microenvironment. Our study investigated for first time the distribution of serglycin in normal epithelial and cancerous lesions in most common cancer types. The elevated levels of serglycin in aggressive cancer and stromal cells may suggest a key role for serglycin in disease progression.
Highlights
Proteoglycans are composed of a specific core protein substituted with one or more covalently linked glycosaminoglycan chains
In agreement with data presented in our previous study [9], serglycin was expressed in minute levels in low aggressive MDA-MB-468 and MCF-7 cells, whereas it was expressed in elevated levels in high aggressive MDA-MD-231 breast cancer cells, which are KRAS38G → A and BRAF1391G → T mutant (Figure 1(a)) [13, 14]
Serglycin is secreted in elevated levels in cancer cells mutated in KRAS or HER1/EGFR, the fact that may suggest an implication of EGFR-RAS pathway in the biosynthesis and more importantly in secretion of serglycin
Summary
Proteoglycans are composed of a specific core protein substituted with one or more covalently linked glycosaminoglycan chains. Proteoglycans are synthesized by tumor and stromal cells and their biosynthesis is often dysregulated in malignancies, providing a favorable microenvironment for disease progression [2]. Serglycin is highly expressed and secreted by tumor cells themselves and its overexpression is associated with tumor cell aggressiveness and poor disease outcome [8,9,10]. It is the major proteoglycan secreted by multiple myeloma cells affecting bone mineralization [7] growth of myeloma cell in BioMed Research International vivo and secretion of hepatocyte growth factor (HGF) [5]. Our findings that serglycin is markedly synthesized by cancer and stromal cells in malignant tissues may propose a role for serglycin in cancer progression
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