To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X, in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100 cases of invasive micropapillary carcinoma and 97 cases of invasive ductal carcinoma were analyzed immunohistochemically for the expression of E-selectin and Sialyl Lewis X, along with CD34, to measure the microvessel density of invasive micropapillary carcinoma. We found that the number of E-selectin-positive vessels was greater in invasive micropapillary carcinoma than in invasive ductal carcinoma, and it was significantly correlated with the histological grade, the number of positive lymph nodes, and the microvessel density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of invasive micropapillary carcinoma was higher than that of invasive ductal carcinoma, which was also associated with lymph node metastasis. In invasive micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the stroma-facing surface of the cell clusters and the adjacent stroma, while in invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These findings suggested that E-selectin and Sialyl Lewis X might play an important role in lymph node metastasis in invasive micropapillary carcinoma. The expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma suggested that the reversal of cell polarity of invasive micropapillary carcinoma might be as an important factor for the morphogenesis and possibly the pathogenesis, especially their higher rates of lymph node metastasis.
"e l s e v i e r . c o m / l o c a t e / y b b r c increased substantially in tumors , including prostate cancers  . Elevated expression of sLe x and sLe a on mucin type O-glycans is highly correlated with lymphatic and venous invasion of cancerous cells [15,16]. "
[Show abstract][Hide abstract] ABSTRACT: Sialyl Lewis x (sLe(x)) plays an important role in cancer metastasis. But, the mechanism for its production in metastatic cancers remains unclear. The objective of current study was to examine the effects of a proinflammatory cytokine on the expression of glycosyltransferase and sulfotransferase genes involved in the synthesis of selectin ligands in a prostate cancer cell line. Androgen-independent human lymph node-derived metastatic prostate cancer cells (C-81 LNCaP), which express functional androgen receptor and mimic the castration-resistant advanced prostate cancer, were used. TNFα treatment of these cells increased their binding to P-, E- and L-selectins, anti-sLe(x) antibody, and anti-6-sulfo-sialyl Lewis x antibody by 12%, 240%, 43%, 248% and 21%, respectively. Also, the expression of C2GnT-1, B4GalT1, GlcNAc6ST3, and ST3Gal3 genes was significantly upregulated. Further treatment of TNFα-treated cells with either anti-sLe(x) antibody or E-selectin significantly suppressed their in vitro migration (81% and 52%, respectively) and invasion (45% and 56%, respectively). Our data indicate that TNFα treatment enhances the motility and invasion properties of LNCaP C-81 cells by increasing the formation of selectin ligands through stimulation of the expression of selective glycosyl- and sulfotransferase genes. These results support the hypothesis that inflammation contributes to cancer metastasis.
Biochemical and Biophysical Research Communications 06/2011; 409(3):436-41. DOI:10.1016/j.bbrc.2011.05.019 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although intravenous administration of high levels of cisplatin (CDDP) are limited due to its severe side effects, efficient delivery of CDDP directly to the tumor should improve the therapeutic response while potentially by-passing significant side effects. High loading of CDDP into liposomes is one technique that could be used as a potential drug delivery system. Since cis-diamminedinitratoplatinum (CDDP3) is highly soluble in water and converts to CDDP in the presence of chloride ions, we encapsulated CDDP3 into liposomes in the absence of chloride ions and supplemented chloride ions to prepare CDDP-encapsulated liposomes (CDDP-Lip) resulting in a significantly improved loading efficiency of CDDP. We further conjugated the CDDP-Lip with Sialyl Lewis(X) (CDDP-SLX-Lip) because we previously demonstrated Sialyl Lewis(X) enhanced efficient accumulation of liposomes into tumors in vivo. CDDP-SLX-Lip treated mice showed a survival rate of 75% at 14 days even if a lethal level of CDDP was injected into mice. Loss of body weight was negligible and no histological abnormality was found in a variety of normal tissues. Accumulation of CDDP-SLX-Lip was about 6 times more than that of CDDP-Lip or CDDP. As the result, there was better antitumor activity of CDDP-SLX-Lip than that of CDDP-Lip with significantly less toxic effects in normal tissues.
International Journal of Pharmaceutics 03/2010; 391(1-2):274-83. DOI:10.1016/j.ijpharm.2010.02.030 · 3.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Breast cancer cells with a CD44(+)/CD24(-/low) phenotype have been suggested to have tumor-initiating properties. It is unclear whether their presence correlates with clinicopathological features of invasive micropapillary carcinoma (IMPC) of the breast, an unusual subtype of breast cancer with a high incidence of lymph node metastasis and poor prognosis. CD44 and CD24 expression was determined by double-staining immunohistochemistry in 103 cases of IMPC and in 94 cases of invasive ductal carcinoma (IDC). The prevalence of CD44(+)/CD24(-/low) tumor cells was higher in IMPC than in invasive ductal carcinoma IDC (P=0.018). The CD44(+)/CD24(-/low) tumor cells were also detected in adjacent stroma surrounding the micropapillary structure in 53.4% (55/103) of IMPC, but only in 7.4% (7/94) of stroma of IDC. These tumor cells in stroma of IMPC were positive for vimentin and α-smooth muscle actin, and negative for E-cadherin. The CD44(+)/CD24(-/low) tumor cells in the micropapillary structure of IMPC were associated with those in stroma (P=0.000). Moreover, they were both associated with lymphovascular invasion and extranodal extension, respectively (P<0.05). The proportion of CD24(+) tumor cells was also higher in IMPC than in IDC (P=0.035), and the CD24(+) tumor cells were associated with lymph node metastasis in IMPC (P=0.010). The results suggest that the increased proportion of CD44(+)/CD24(-/low) tumor cells and CD24(+) tumor cells and the epithelial mesenchymal transition may play an important role in aggressiveness and high metastatic risk of breast IMPC.
Pathology - Research and Practice 10/2010; 206(12):828-34. DOI:10.1016/j.prp.2010.09.008 · 1.40 Impact Factor
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