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M J Stanley

Publications and source records attributed to M J Stanley.

9 recordsLinked to original sources
PubMed1999

Syndecan-1 expression is induced in the stroma of infiltrating breast carcinoma.

Loss of expression of the heparan sulfate proteoglycan syndecan-1 leads to reduced cell adhesion, increased invasive potential, and dysregulated growth of mammary epithelial cells in vitro. We compared syndecan-1 expression in malignant and nonmalignant breast tissues using immunohisto-chemistry with monoclonal antibody B-B4. Staining for syndecan-1 is greatly diminished on malignant cells within infiltrating ductal carcinomas (n = 20) as compared with ductal epithelium of both normal breast (n = 14) and stromal-epithelial neoplasms (n = 10), which exhibit extensive basolateral epithelial staining. Surprisingly, comparison of malignant and nonmalignant breast tissue also reveals a striking difference in expression of syndecan-1 within the stromal compartment. In infiltrating ductal carcinomas, strong staining for syndecan-1 is present both within the connective tissue and on stromal cell surfaces, whereas syndecan-1 expression is absent in the stroma of both normal breast and stromal-epithelial neoplasms. Because syndecan-1 interacts with heparin-binding growth factors such as FGF-2, accumulation of syndecan-1 within the tumor stroma may contribute to the extensive angiogenesis and stromal proliferation characteristic of infiltrating breast carcinoma. Moreover, the induction of syndecan-1 within the stroma, coupled with the loss of syndecan-1 on malignant cells, suggests that changes in syndecan-1 expression are critical in promoting the metastatic phenotype of infiltrating ductal carcinoma of the breast.

Breast Neoplasms↗
PubMed1998

Multiple heparan sulfate chains are required for optimal syndecan-1 function.

Syndecans have three highly conserved sites available for heparan sulfate attachment. To determine if all three sites are required for normal function, a series of mutated syndecans having two, one, or no heparan sulfate chains were expressed in ARH-77 cells. Previously, we demonstrated that expression of wild-type syndecan-1 on these myeloma cells mediates cell-matrix and cell-cell adhesion and inhibits cell invasion into collagen gels. Here we show that to optimally mediate each of these activities, all three sites of heparan sulfate attachment are required. Generally, an increasing loss of syndecan-1 function occurs as the number of heparan sulfate attachment sites decreases. This loss of function is not the result of a decrease in either the total amount of cell surface heparan sulfate or syndecan-1 core protein. In regard to cell invasion, cells expressing syndecan-1 bearing a single heparan sulfate attachment site exhibit a hierarchy of function based upon the position of the site within the core protein; the presence of an available attachment site at serine 47 confers the greatest level of activity, while serine 37 contributes little to syndecan-1 function. However, when all three heparan sulfate chains are present, significantly greater biological activity is observed than is predicted by the sum of the activities occurring when the chains act individually. This synergy provides a functional basis for the evolutionary conservation of the three heparan sulfate attachment sites on syndecans and supports the idea that molecular heterogeneity, which is characteristic of proteoglycans, contributes to their functional diversity.

Cell Adhesion↗
PubMed1998

Heparan sulfate proteoglycans as adhesive and anti-invasive molecules. Syndecans and glypican have distinct functions.

ARH-77 cells do not adhere to type I collagen and readily invade into collagen gels, but following expression of the transmembrane heparan sulfate proteoglycan syndecan-1, they bind collagen and fail to invade. We now show that cells transfected with syndecan-2 or syndecan-4 also bind collagen and are non-invasive. In contrast, cells transfected with the glycosylphosphatidylinositol-anchored proteoglycan glypican-1 do not bind to collagen and remain invasive, even though glypican- and syndecan-expressing cells have similar surface levels of heparan sulfate, and their proteoglycans have similar affinities for collagen. Analysis of cells expressing syndecan-1-glypican-1 chimeric proteoglycans reveals that inhibition of invasion requires the extracellular domain of syndecan but not its transmembrane or cytoplasmic domain. Surprisingly, cells bearing a chimera composed of the glypican extracellular domain fused to the syndecan transmembrane and cytoplasmic domains bind to collagen but remain invasive, implying that adhesion to collagen is not by itself sufficient to inhibit invasion. Apparently, the extracellular domain of syndecan-1, presumably by interacting with cell-surface signal transducing molecules, directly regulates complex cell behaviors such as motility and invasiveness. These results also show for the first time that syndecans and glypicans can have distinct functions, even when expressed by the same cell type.

Animals↗
PubMed1995

Heparan sulfate-mediated cell aggregation. Syndecans-1 and -4 mediate intercellular adhesion following their transfection into human B lymphoid cells.

Because syndecans are present at sites of cell-cell contact in vivo it has been hypothesized that they play a role in mediating cell-cell adhesion. However, there has been no direct evidence to support this notion. To address this question, B lymphoid (ARH-77) cells were transfected with the cDNA for murine syndecan-1. Unlike the parental cells, the transfectants form large multicellular aggregates in suspension cultures and stain intensely for syndecan-1 at sites of cell-cell contact. Using rotation-mediated aggregation assays, we find that aggregation of syndecan-1-transfected cells is dependent on divalent cations and is inhibited by the following: (i) addition of heparin and heparin-like glycosaminoglycans, (ii) removal of heparan sulfate from the cell surface, or (iii) addition of exogenous purified syndecan-1. Mixing of syndecan-1-transfected and control-transfected cells results in aggregates containing both cell types indicating that aggregation occurs through a heterophilic adhesion mechanism in which heparan sulfate chains bind to a counter-receptor present on these cells. Importantly, syndecan-4-transfected cells also aggregate in a heparan sulfate-dependent manner, while in contrast, betaglycan-transfected cells aggregate poorly. Thus, syndecans may be important mediators of cell-cell adhesion, but this function may not be common to all transmembrane heparan sulfate-bearing proteoglycans.

Animals↗
PubMed1988

Adjustment problems of spouses of patients undergoing coronary artery bypass graft surgery during early convalescence.

Our purpose was to assess the social adjustment of spouses of patients who had undergone coronary artery bypass surgery during the patients' early convalescence. Specifically the study focused on social support and social activities, affective responses, and financial, marital, and sexual difficulties. Following an exploratory descriptive design, we conducted a semistructured interview using Benson's (1984) Social Adjustment Scale. A sample of 26 spouses were interviewed in a cardiology clinic 4 to 10 weeks after their mate's bypass surgery. Associations between demographic characteristics and the level of adjustment were determined by chi-square (adjusted for continuity) analysis. Nineteen spouses reported a high level of vigilance, with 13 reporting that this was a change since their mate's surgery. Ten spouses reported their economic level to be highly inadequate, and all of those stated that their economic situation had changed since surgery. A small number of subjects rated their mate as being dependent on them, and they had feelings of anxiety, fear, and depression. All of those subjects described this as a change since surgery. The majority of subjects had a low level of marital friction and a high level of communication with their spouse. Those married 30 years or longer were generally those satisfied with their level of social support.

Adult↗