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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcomas and rhabdomyosarcomas are vigorously invading tumors. Before they can extravasate to the parenchymal organs and form metastases, they have to adhere to the endothelial cells lining the blood vessels and then penetrate through the endothelium. We show that several human sarcoma cell lines, osteosarcomas HOS, MG-63, U2-OS, and a rhabdomyosarcoma RD, express VLA-4 molecule on their surface and bind to the VCAM-I-expressing activated endothelial cell line Ea.hy 926. The increased sarcoma-cell adhesion could be abolished by treating the sarcoma cells with monoclonal antibodies (MAbs) VLA4 (both alpha- and beta-chain, HP2/1 and 4B4 respectively) or treating endothelial cells with VCAM-I antibody (4B9). Furthermore, we show that sarcoma cells adhere to recombinant soluble VCAM-I protein. On the other hand, these sarcoma cell lines do not express marked amounts of other ligands (such as CDII/18 or sialyl-Lex) for other endothelial adhesion molecules (ICAM-I, ICAM-2, E- and P-selectin) indicating that the VLA-4-VCAM-I dependent pathway might be of major importance in sarcoma extravasation. VLA-4 is not always in an avid form and therefore the expression of VLA-4 does not directly predict adherence to VCAM-I. The avidity of VLA-4 (measured by adherence to soluble VCAM-I) of MG-63 and U2-OS cells could be increased by a 30-min PMA treatment, whereas the avidity of VLA-4 on HOS cells increased only after 48 hr of PMA induction. Our results show that sarcoma cell lines (HOS, MG-63, U2-OS and RD) adhere to stimulated endothelium via VLA-4-VCAM-I adhesion molecules and that VLA-4 avidity on sarcoma cells can be differentially modulated by PMA.
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PMID:VLA-4 integrin on sarcoma cell lines recognizes endothelial VCAM-1. Differential regulation of the VLA-4 avidity on various sarcoma cell lines. 128 Nov 43

We have previously shown that the degree of expression of Lex-related carbohydrate epitopes, namely, Lotus tetragonolobus agglutinin (LTA) receptors, SSEA-1 and FH6, correlates with the metastatic potential of transitional cell carcinoma of the human urinary bladder. In an effort to obtain a better reagent with which to detect a metastasis-associated epitope, monoclonal antibodies were produced against LTA receptors from BOY bladder carcinoma cells. One antigen defined by such a monoclonal antibody, MM4, indeed showed better correlation with the metastatic potential of the tumour than did other carbohydrate markers. In the LTA receptors, MM4 antigen was located only on a 60 kDa glycoprotein. In extracts from primary carcinomas and lymph node metastases, the 60 kDa glycoprotein was the principal carrier of MM4 antigen. LTA receptors from these sources were composed of arrays of glycoproteins, while the 60 kDa one was invariably present. Metastasis-associated carbohydrate epitopes on the 60 kDa glycoprotein may promote metastasis by interaction with carbohydrate-recognizing proteins such as selectins on host cells.
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PMID:A metastasis-associated antigen is present on a 60 kDa glycoprotein in transitional cell carcinoma of the human urinary bladder. 147 89

Essentially all tumors express aberrantly glycosylated glycosphingolipids and glycoproteins, more commonly known as "tumor-associated carbohydrate antigens." In this article I propose two new forms of cancer therapy, anti-adhesion therapy and ortho-signaling therapy, which exploit these tumor-associated carbohydrates in distinct ways. The aim of anti-adhesion therapy is to disrupt the requisite carbohydrate-initiated interactions that occur between tumor cells and other cell types (e.g., endothelial cells, platelets) as tumors progress and metastasize. Candidate anti-adhesion agents include purified carbohydrates or glycosphingolipids representing H, Ley, sialosyl-Lex (or -Lea) GM3, or LacCer antigens, and monoclonal antibodies directed to these structures. The aim of ortho-signaling therapy is to disrupt mitogenic signaling pathways in tumor cells that are regulated by glycosphingolipids and/or their derivatives, including pathways involving receptor protein-kinases and protein kinase C. Candidate ortho-signaling agents are the glycosphingolipid regulator PDMP (1-phenyl-2-[decanoylamino]-3-morpholino-1-propanol) and the protein kinase C inhibitor DMS (N,N-dimethylsphingosine), both of which show antitumor activity in vitro and in animal studies.
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PMID:New directions in cancer therapy based on aberrant expression of glycosphingolipids: anti-adhesion and ortho-signaling therapy. 182 92

Colorectal primary carcinomas and metastases from 20 Dukes' stage C or D patients were examined for the immunohistochemical localization and contents of various fucosylated N-acetyl-lactosamine oligomers by specific monoclonal antibodies (MAbs). MAbs used were SH1, specific for Lewis X antigen; FH4, specific for dimeric Lewis X antigen; FH6, specific for sialyl-dimeric Lewis X antigen; and KH1, specific for Lewis Y-Lewis X antigen. The distribution of the carbohydrate antigens identified by these MAbs was heterogeneous within the primary tumor as well as within the metastatic lesion. Examinations of serial sections indicated that areas within an individual tumor which were stained with one MAb were not always reactive with the other MAbs, although these four MAbs identify closely related structures. The degree of MAb reactivity with carcinoma sections was classified by percentage positive carcinoma cells, and primary tumors and metastases from the same patients were compared. An equivalent or higher proportion of carcinoma cells in the metastatic lesions were reactive with MAb FH6 than in the primary colon carcinomas, but each correlation was not seen with the other MAbs. Electrophoretic separation of tumor tissue extracts followed by staining with these MAbs revealed that a component having an approximate molecular weight of 1,000,000 is the major site for the binding of MAbs, FH6, FH4, and KH1. The electrophoretic mobility of the antigenic molecule on polyacrylamide gels as shown by direct MAb bindings was slightly different from that of a major sialomucin revealed by wheat germ agglutinin in the same tissues. MAb FH6 binding to a high molecular weight component was eliminated by prior treatment of the glycoprotein with mild acid or sialidase to remove sialic acid. Simultaneously, binding of MAb SH2, specific for dimeric Lex antigen, to this component increased. An extract was prepared from a liver metastasis, and high molecular weight components were isolated by gel filtration and then fractionated by DEAE-cellulose ion exchange chromatography. A fraction eluted from DEAE-cellulose between 0.10-0.25 M sodium chloride contained most of the MAb FH6 reactivity, as shown by antibody affinity chromatography. These results support a hypothesis that high molecular weight glycoproteins produced by colorectal carcinoma tissues are heterogeneous with regard to their carbohydrate chains and their antigenic structures may change during tumor progression.
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PMID:Sialyl-dimeric Lewis-X antigen expressed on mucin-like glycoproteins in colorectal cancer metastases. 197 61

The recognition of an adhesive role for the CEA-related antigens emphasizes the need for clear demonstration of the changes in CEA expression and subcellular localization between normal and neoplastic tissues. Using a panel of monoclonal and polyclonal antibodies, membranous and cytoplasmic CEA expression was seen in 50 invasive cervical squamous carcinomas in four distinct patterns dependent on tumour type and differentiation. Membranous CEA expression is a marker of differentiation in squamous carcinomas and may influence tumour behaviour and hence patient survival. Strong CEA positivity was seen on the endothelium of vessels containing tumour in ten cases where vascular metastases were prominent. Staining of these ten cases revealed concomitant sialated Lewis X positivity in tumour cells with weak endothelial positivity in three cases; cervical squamous tumour cells may localize to vascular endothelium, and hence disseminate, through specific binding of CEA and/or sialated Lewis X.
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PMID:Patterns of CEA-related antigen expression in invasive squamous carcinoma of the cervix. 790 54

A case of mucinous cholangiocarcinoma is reported. The patient was a 49 year old woman with the complaint of lumbago. Imaging examination disclosed a tumor 3.5 cm in diameter in the right hepatic lobe, which showed low density on computerized tomography scans and low signal intensity on T1-weighted magnetic resonance imaging (MRI) and high intensity on T2-weighted MRI. The hepatic tumor expanded rapidly and multiple pulmonary metastases and peritoneal dissemination developed. The patient died due to respiratory failure 5 months after the initial symptom. An autopsy, a massive tumor (9.5 cm in diameter) containing abundant mucus with several surrounding daughter nodules was found in the right hepatic lobe. Metastases were widespread. Histologically, the tumor was composed mainly of numerous lobulated mucus lakes in which adenocarcinoma cells floated. Admixed signet ring cells were also noted. These gross and histologic features differ from those in other mucin-producing hepatic tumors such as biliary papillomatosis and mucinous cystoadenocarcinoma. Immunohistochemically, the adenocarcinoma cells were strongly positive for carcinoembryonic antigen, Lewis Y, Tn, and T antigens and moderately positive for carbohydrate antigen 19-9, Lewis X, sialyl-Lewis X and sialyl-Tn antigen. Mature MUC1 mucin and core protein of MUC1 mucin were also expressed to varying degrees. The rapidly expanding, widespread metastases and poor prognosis found in the present case may be the clinicopathological features of mucinous cholangiocarcinoma.
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PMID:Pathological and immunohistochemical findings in a case of mucinous cholangiocarcinoma. 856 41

Sialyl Lewis A (SLA) and sialyl Lewis X (SLX) have been shown to be specific ligands for endothelial leukocyte adhesion molecule-1 (ELAM-1), and may be involved in the process of adhesion between cancer cells and endothelium. We used immunohistochemical methods to study the expression of SLA, SLX and CEA in both primary tumors and matched metastatic liver lesions of colorectal carcinomas. Specimens from primary tumors and matched liver metastases from 24 patients with colorectal carcinomas were studied immunohistochemically. The degree of expression of CEA in liver metastases was similar to that in primary tumors, but SLA and SLX were expressed on a larger proportion of tumor cells in liver metastases than in primary tumors. Our findings suggest that colorectal carcinoma cells expressing SLA and/or SLX form metastatic liver tumors. They also suggest that expression of SLA and SLX in primary of colorectal carcinoma can be used as a prognostic indicator of metastasis.
Invasion Metastasis 1995
PMID:Increased expression of sialyl Lewis A and sialyl Lewis X in liver metastases of human colorectal carcinoma. 862 Dec 74

Metastasis accounts for most of deaths caused by cancer. The increasing body of evidence suggests that changes in N-glycosylation of tumor cell proteins such as increased branching, increased sialylation, polysialylation, decreased fucosylation, enhanced formation of Lewis X and sialyl Lewis X antigens are among important factors determining metastatic potential of tumor cell. Most of the adhesion proteins, e.g., integrins, members of immunoglobulin superfamily, and cadherins are heavily N-glycosylated. The other proteins involved in adhesion, like galectins and type-C selectins, recognize N-glycans as a part of their specific ligands. In this review we focus on recent reports concerning the contribution of N-glycosylation of tumor cell adhesion molecules and some selected membrane proteins in the tumor invasion and metastasis.
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PMID:Tumor cell N-glycans in metastasis. 936 Jul 25

Two anti-sialyl Lewis X (sLeX) monoclonal antibodies, mAb FH6 and mAb KM93, were analyzed by flow cytometry for their ability to bind to 16 human colon carcinoma cells. The binding profiles of these two anti-sLeX monoclonal antibodies did not correspond to each other. Three of the cell lines were reactive with mAb FH6 but not with mAb KM93. These three cell lines did not adhere to Chinese hamster ovary cells that were stably transfected with human E-selectin cDNA in an E-selectin-dependent manner. In contrast, almost all human colon carcinoma cell lines that bound to mAb KM93 adhered to cells that expressed E-selectin. These results suggest that a subtype of sLeX carbohydrate epitopes recognized by mAb FH6 do not always function as ligands for E-selectin.
Clin Exp Metastasis 1998 Aug
PMID:Comparison of 16 human colon carcinoma cell lines for their expression of sialyl LeX antigens and their E-selectin-dependent adhesion. 987 4

We have previously reported that colon cancer cells metastasized to the liver expressed an increased amount of sialyl Lewis X (SLeX) antigen compared to their corresponding primary lesions. It is now well known that SLeX antigen and sialyl Lewis A (SLeA) antigen are ligands for the selectins expressed on the endothelial cells. Therefore, it is assumed that SLeX-rich colon cancer cells could be easily adhered to the endothelial cells that express selectins. In this report we have tried to induce selectin expression on the human liver sinusoidal endothelial cells and have examined the adhesion of SLeX-high or -low expressing colon cancer cells to the interleukin-1beta (IL-1beta)-treated liver specimens using Stamper-Woodruff assay. These human colon cancer cells are termed KM12HX or KM12LX cells, respectively. A significantly increased number of KM12HX cells adhered to the IL-1beta-treated liver specimens compared to KM12LX cells. The adhesion of KM12HX cells was inhibited by the pretreatment of tumor cells with anti-SLeX antibody or by the pretreatment of liver specimens with anti-selectin antibodies. Selectin expression on the liver sinusoidal endothelial cells and endothelial cells of blood vessels after IL-1beta treatment was confirmed by immunohistochemically using anti-selectin monoclonal antibodies (MAbs). These findings strongly suggest that SLeX-expressing cancer cells could adhere to the sinusoidal endothelial cells via an SLeX-selectin interaction system and this could be a first step for colon cancer cells that metastasize to the liver. The mechanism by which these selectins can be induced in vivo is the next problem to be considered.
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PMID:Selectins induced by interleukin-1beta on the human liver endothelial cells act as ligands for sialyl Lewis X-expressing human colon cancer cell metastasis. 1007 64


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