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Serglycin is implicated in the promotion of aggressive phenotype of breast cancer cells.

Korpetinou A, Skandalis SS, Moustakas A, Happonen KE, Tveit H, Prydz K, Labropoulou VT, Giannopoulou E, Kalofonos HP, Blom AM, Karamanos NK, Theocharis AD - PLoS ONE (2013)

Bottom 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.

ABSTRACT
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.

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Immunohistochemical reactivity of serglycin in normal breast and breast carcinoma.Normal epithelial breast cells in mammary glands were moderately reactive with the polyclonal antibody against serglycin and the reactivity was cytoplasmic (A). Breast cancer cells were stained strongly for serglycin in grade 2 breast carcinomas (B–D). The serglycin reactivity was mainly cytoplasmic, although in some cases cell-surface associated staining was detected in breast cancer cells (D, arrowheads and insert). Bars, 50 µm.
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pone-0078157-g001: Immunohistochemical reactivity of serglycin in normal breast and breast carcinoma.Normal epithelial breast cells in mammary glands were moderately reactive with the polyclonal antibody against serglycin and the reactivity was cytoplasmic (A). Breast cancer cells were stained strongly for serglycin in grade 2 breast carcinomas (B–D). The serglycin reactivity was mainly cytoplasmic, although in some cases cell-surface associated staining was detected in breast cancer cells (D, arrowheads and insert). Bars, 50 µm.

Mentions: The expression of serglycin in normal breast tissue and breast carcinoma was examined by immunohistochemistry in paraffin-embedded tissues. Using a polyclonal antibody, serglycin was found to be expressed by normal epithelial cells in mammary glands of healthy tissues (Fig. 1A) showing a moderate cytoplasmic staining. Notably, serglycin was ubiquitously synthesized by breast cancer cells, in all cases showing a strong cytoplasmic staining (Fig. 1B–D). In some cases, cell membrane-associated reactivity for serglycin was also apparent (Fig. 1D, arrowheads).


Serglycin is implicated in the promotion of aggressive phenotype of breast cancer cells.

Korpetinou A, Skandalis SS, Moustakas A, Happonen KE, Tveit H, Prydz K, Labropoulou VT, Giannopoulou E, Kalofonos HP, Blom AM, Karamanos NK, Theocharis AD - PLoS ONE (2013)

Immunohistochemical reactivity of serglycin in normal breast and breast carcinoma.Normal epithelial breast cells in mammary glands were moderately reactive with the polyclonal antibody against serglycin and the reactivity was cytoplasmic (A). Breast cancer cells were stained strongly for serglycin in grade 2 breast carcinomas (B–D). The serglycin reactivity was mainly cytoplasmic, although in some cases cell-surface associated staining was detected in breast cancer cells (D, arrowheads and insert). Bars, 50 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815026&req=5

pone-0078157-g001: Immunohistochemical reactivity of serglycin in normal breast and breast carcinoma.Normal epithelial breast cells in mammary glands were moderately reactive with the polyclonal antibody against serglycin and the reactivity was cytoplasmic (A). Breast cancer cells were stained strongly for serglycin in grade 2 breast carcinomas (B–D). The serglycin reactivity was mainly cytoplasmic, although in some cases cell-surface associated staining was detected in breast cancer cells (D, arrowheads and insert). Bars, 50 µm.
Mentions: The expression of serglycin in normal breast tissue and breast carcinoma was examined by immunohistochemistry in paraffin-embedded tissues. Using a polyclonal antibody, serglycin was found to be expressed by normal epithelial cells in mammary glands of healthy tissues (Fig. 1A) showing a moderate cytoplasmic staining. Notably, serglycin was ubiquitously synthesized by breast cancer cells, in all cases showing a strong cytoplasmic staining (Fig. 1B–D). In some cases, cell membrane-associated reactivity for serglycin was also apparent (Fig. 1D, arrowheads).

Bottom 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.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus