alpha-Neup5Ac-(2--3)-beta-D-Galp-(1--4)-[alpha-L-Fucp-(1--3)]-D-GlcpNAc and Peritoneal-Neoplasms

Expression of sialyl-Lewisx (sLex) antigen was studied immunohistochemically in 110 resected human gastric carcinomas using an anti-sLex monoclonal antibody. Lymph node, liver, and peritoneal metastases were clearly more prevalent in tumors expressing high levels of sLex than in those with no or low-level sLex expression. No correlation was found between sLex expression and histologic grade or histologic type of the Lauren classification. Among the tumors with lymph node metastasis, 44% expressed high levels of sLex in both the primary tumor and involved lymph nodes, and 14% of the metastatic lesions demonstrated increased sLex expression. The 5-year survival rate of the patients undergoing complete (R0) gastric resections was 60% in the sLex high-expression group, which was significantly lower than that of the sLex low-expression group (81%) and of the no-expression group (87%) (p < 0.05). These results suggest that high-level sLex expression is related to both an increased risk of metastasis and poor prognosis in gastric cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Gastrectomy; Humans; Immunohistochemistry; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Metastasis; Oligosaccharides; Peritoneal Neoplasms; Prognosis; Risk; Sialyl Lewis X Antigen; Stomach Neoplasms; Survival Rate

Organ-specific colonization suggests that specific cell-cell recognition is essential. Yet, very little is known about this particular interaction. Moreover, tumor cell lodgement requires binding under shear stress, but not static, conditions. Here, we successfully isolate the metastatic populations of cancer stem/tumor-initiating cells (M-CSCs). We show that the M-CSCs tether more and roll slower than the non-metastatic (NM)-CSCs, thus resulting in the preferential binding to the peritoneal mesothelium under ascitic fluid shear stress. Mechanistically, this interaction is mediated by P-selectin expressed by the peritoneal mesothelium. Insulin-like growth factor receptor-1 carrying an uncommon non-sulfated sialyl-Lewis

Topics: Animals; Ascitic Fluid; Carcinoma; Cell Adhesion; Cell Line, Tumor; Epithelium; Female; Fucosyltransferases; HEK293 Cells; Humans; Hydrodynamics; Mice; Neoplasm Metastasis; Neoplasm Transplantation; Neoplastic Stem Cells; Oligosaccharides; Ovarian Neoplasms; P-Selectin; Peritoneal Neoplasms; Peritoneum; Receptor, IGF Type 1; Sialyl Lewis X Antigen; Stress, Mechanical

Carbohydrate expression of cancer cells is closely related to the metastatic nature of colorectal cancer. In the present study we investigated the relevance of carbohydrate expression profiles of colorectal cancer cells in the primary lesion to metastatic distribution patterns as well as prognosis in 134 cases. Carbohydrate expression was estimated by histochemistry with 17 kinds of lectins and 3 kinds of Lewis-related monoclonal antibodies (MAbs), and correlations between the staining and clinicopathological parameters were examined. The results showed that lymphatic invasion, lymph node metastasis, and peritoneal metastasis correlated with staining with lectins that bind galactose/N-acetylgalactosamine residues (Gal/GalNAc) such as Maclura pomifera (MPA), Arachis hypogaea (PNA), Helix pomatia (HPA), and Vicia villosa (VVA). In contrast, hepatic metastasis correlated with staining with Anguilla anguilla lectin (AAA), anti-LewisX (LEX-2), anti-sialyl Lewisa (NS 19-9), and anti-sialyl-dimeric LewisX (FH-6) MAbs, all of which bind preferentially to fucosylated carbohydrate chains. The five-year survival rate of patients was related to the staining of cancers with MPA, HPA, FH-6 or NS19-9, and MPA- and FH-6 staining were independent prognostic factors. We conclude that carbohydrate expression profiles of cancer cells are relevant to the route of tumor cell dissemination, metastatic pattern as well as prognosis of colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; Antigens, Neoplasm; Carbohydrate Metabolism; Carbohydrate Sequence; Carbohydrates; Colorectal Neoplasms; Female; Humans; Lectins; Lewis X Antigen; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Molecular Sequence Data; Neoplasm Invasiveness; Neoplasm Metastasis; Oligosaccharides; Peritoneal Neoplasms; Prognosis; Prospective Studies; Sialyl Lewis X Antigen; Staining and Labeling

Several alpha(1,3/1,4) fucosyltransferases expressed in human pancreatic cancer cells can participate in the biosynthesis of cell surface sialyl-Lewis a and sialyl-Lewis x antigens that contribute to hematogenous metastatis. Previously, we observed a significant increase of the alpha(1,4) fucosyltransferase activity in tumoral pancreatic cell lines, suggesting that FUT3 could be involved in the sialyl-Lewis antigen expression. Therefore, we invalidated the expression of FUT3 by expressing FUT3 antisense sequence in the human pancreatic tumor BxPC-3 cell line, which expresses the alpha(1,4) fucosyltransferase activity and harbors the cell surface sialyl-Lewis antigens. The decrease of FUT3 transcript after transfection of antisense cDNA of FUT3 in these cells results in a substantial reduction of sialyl-Lewis antigen expression on cell surface. This decreased antigen expression was associated with an inhibition of adhesive properties to E-selectin and a decrease of metastatic power of FUT3 antisense-transfected BxPC-3 cells as tested in nude mice. Our study provides evidence that the expression level of FUT3 may regulate the expression of sialyl-Lewis a and sialyl-Lewis x surface antigens and consequently could play an important role in metastatic properties of human pancreatic cancer cells.

Topics: Animals; CHO Cells; Cricetinae; E-Selectin; Female; Fucosyltransferases; Humans; Mice; Mice, Nude; Oligosaccharides; Pancreatic Neoplasms; Peritoneal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Antisense; RNA, Messenger; Sialyl Lewis X Antigen; Transcription, Genetic; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Sialyl Lewis(x)antigen (SLX) is a carbohydrate antigen that serves as a ligand for selectin, an adhesion molecule expressed on vascular endothelial cells. The expression of SLX in 245 patients with advanced gastric carcinoma was examined immunohistochemically, and its clinicopathologic significance was analysed. We classified the patients with advanced gastric carcinoma into 91 with differentiated type and 154 with undifferentiated type. SLX expressed in 135 of 245 patients (55%), comprising 68 (75%) patients with differentiated carcinoma and 67 (44%) with undifferentiated carcinoma. The positive rate for SLX expression was significantly higher among patients with differentiated carcinoma than among those in undifferentiated carcinoma (P<0.0001). With differentiated carcinoma, the incidence of lymph node metastasis, advanced tumour stage (stage III and IV) and liver recurrence was significantly higher in SLX-positive patients than in SLX-negative ones (P<0.0001, P = 0.0065 and P = 0. 028, respectively). Moreover, the prognoses were better in patients with SLX-negative tumours than in those with SLX-positive tumours (P = 0.019). With undifferentiated carcinoma, there were no significant correlations between SLX expression and any clinicopathological features or prognoses. The clinicopathologic significance of SLX expression in gastric carcinoma patients depends on histologic type. SLX expression may be of great relevance in predicting liver metastases in patients with differentiated carcinoma.

Topics: Aged; Carcinoma; Female; Humans; Immunohistochemistry; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oligosaccharides; Peritoneal Neoplasms; Sialyl Lewis X Antigen; Stomach Neoplasms; Survival Analysis

Ten human colorectal cancer (CRC) cell lines were implanted orthotopically into the ceca and also into the livers, muscles and peritoneal cavities of SCID mice in order to analyze the characteristics regulating metastatic behaviors of CRCs. All the CRC cell lines formed tumors in the muscle and cecum, but they could be classified into two groups: (1) six cell lines with high tumorigenicity in the liver (HTLs) forming differentiated tumors, and (2) four with no tumorigenicity in the liver (NTLs) forming poorly differentiated tumors in SCID mice. After orthotopic implantation, NTLs never metastasized to the liver, whereas HTLs did. Therefore, intrahepatic tumorigenicity and differential status were closely associated with liver metastasis whereas differentiation was not associated with lung metastasis. The 6 HTLs demonstrated an inverse correlation between liver metastases and peritoneal dissemination, and immunohistochemistry indicated expression of sLeX, CA19-9 and carcinoembryonic antigen in tumors which correlated well with the liver metastatic rate. We found a strong correlation between liver metastasis and intrahepatic tumorigenicity and could reproduce the clinical correlations between the pattern of the metastatic spread and the differentiation phenotype of CRC in vivo. We consider further examination using this model will be useful for analyzing the complex mechanisms involved in clinically metastasizing CRCs.

Topics: Adenocarcinoma; Animals; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Carcinogenicity Tests; Colorectal Neoplasms; Disease Models, Animal; ErbB Receptors; Humans; Injections, Intraperitoneal; Liver Neoplasms; Male; Mice; Mice, SCID; Neoplasm Transplantation; Oligosaccharides; Peritoneal Neoplasms; Sialyl Lewis X Antigen; Tumor Cells, Cultured