scholarly journals Metastatic potential severely altered by changes in tumor cell adhesiveness and cell-surface sialylation.

1983 ◽  
Vol 157 (1) ◽  
pp. 371-376 ◽  
Author(s):  
M Fogel ◽  
P Altevogt ◽  
V Schirrmacher
Keyword(s):  
Sialic Acid ◽  
Cell Surface ◽  
Tumor Cell ◽  
Metastatic Potential ◽  
Lectin Receptors ◽  
Lectin Receptor ◽  
Receptor Sites ◽  
Variant Line

A plastic adherent variant line (ESb-M) of a highly invasive and metastatic murine T cell lymphoma (ESb) was found to have lost its metastatic potential while still being tumorigenic in normal syngeneic hosts. The variant retained most of its ESb-derived antigenic and biochemical characteristics but differed at binding sites for certain lectins with specificity for terminal N-acetylgalactosamine residues. Whereas such sites were masked by sialic acid on metastatic ESb cells, they became unmasked on the adherent variant line. Metastatic revertants of ESb-M cells did not express the respective lectin receptor sites because these were again masked by sialic acid. It is suggested that the masking of specific lectin receptors sites on the tumor cell surface is of crucial importance for metastatis. If freely exposed, these sites may change adherence characteristics of the cells possibly not only in vitro (to plastic) but also in vivo.

scholarly journals Induction of Apoptosis of Metastatic Mammary Carcinoma Cells In Vivo by Disruption of Tumor Cell Surface CD44 Function

1997 ◽  
Vol 186 (12) ◽  
pp. 1985-1996 ◽  
Author(s):  
Qin Yu ◽  
Bryan P. Toole ◽  
Ivan Stamenkovic
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Lung Tissue ◽  
Mammary Carcinoma ◽  
Cell Types ◽  
Pulmonary Endothelium ◽  
Soluble Cd44

To understand how the hyaluronan receptor CD44 regulates tumor metastasis, the murine mammary carcinoma TA3/St, which constitutively expresses cell surface CD44, was transfected with cDNAs encoding soluble isoforms of CD44 and the transfectants (TA3sCD44) were compared with parental cells (transfected with expression vector only) for growth in vivo and in vitro. Local release of soluble CD44 by the transfectants inhibited the ability of endogenous cell surface CD44 to bind and internalize hyaluronan and to mediate TA3 cell invasion of hyaluronan-producing cell monolayers. Mice intravenously injected with parental TA3/St cells developed massive pulmonary metastases within 21–28 d, whereas animals injected with TA3sCD44 cells developed few or no tumors. Tracing of labeled parental and transfectant tumor cells revealed that both cell types initially adhered to pulmonary endothelium and penetrated the interstitial stroma. However, although parental cells were dividing and forming clusters within lung tissue 48 h following injection, >80% of TA3sCD44 cells underwent apoptosis. Although sCD44 transfectants displayed a marked reduction in their ability to internalize and degrade hyaluronan, they elicited abundant local hyaluronan production within invaded lung tissue, comparable to that induced by parental cells. These observations provide direct evidence that cell surface CD44 function promotes tumor cell survival in invaded tissue and that its suppression can induce apoptosis of the invading tumor cells, possibly as a result of impairing their ability to penetrate the host tissue hyaluronan barrier.

scholarly journals Galectin-3 Regulates the Expression of Tumor Glycosaminoglycans and Increases the Metastatic Potential of Breast Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Jonathas Xavier Pereira ◽  
Sofia Nascimento dos Santos ◽  
Thaís Canuto Pereira ◽  
Mariana Cabanel ◽  
Roger Chammas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Surface ◽  
Cancer Progression ◽  
Metastatic Potential ◽  
Migration Ability ◽  
Tumor Cell Migration ◽  
Galectin 3 ◽  
4T1 Cells

Galectin-3 (Gal-3) is a multifunctional β-galactoside-binding lectin that once synthesized is expressed in the nucleus, cytoplasm, cell surface, and extracellular environment. Gal-3 plays an important role in breast cancer tumors due to its ability to promote interactions between cell-cell and cell-extracellular matrix (ECM) elements, increasing tumor survival and metastatic dissemination. Still, the mechanism by which Gal-3 interferes with tumor cell migration and metastasis formation is complex and not fully understood. Here, we showed that Gal-3 knockdown increased the migration ability of 4T1 murine breast cancer cells in vitro. Using the 4T1 orthotopic breast cancer spontaneous metastasis mouse model, we demonstrated that 4T1-derived tumors were significantly larger in the presence of Gal-3 (scramble) in comparison with Gal-3 knockdown 4T1-derived tumors. Nevertheless, Gal-3 knockdown 4T1 cells were outnumbered in the bone marrow in comparison with scramble 4T1 cells. Finally, we reported here a decrease in the content of cell-surface syndecan-1 and an increase in the levels of chondroitin sulfate proteoglycans such as versican in Gal-3 knockdown 4T1 cells both in vitro and in vivo. Overall, our findings establish that Gal-3 downregulation during breast cancer progression regulates cell-associated and tumor microenvironment glycosaminoglycans (GAGs)/proteoglycans (PG), thus enhancing the metastatic potential of tumor cells.

The level of cell surface beta1,4-galactosyltransferase I influences the invasive potential of murine melanoma cells

1999 ◽  
Vol 112 (16) ◽  
pp. 2785-2795
Author(s):  
F.M. Johnson ◽  
B.D. Shur
Keyword(s):  
Cell Surface ◽  
Metastatic Potential ◽  
Invasive Potential ◽  
Metastatic Cells ◽  
Metastatic Behavior ◽  
Elevated Expression ◽  
Murine Melanoma Cells ◽  
Galactosyltransferase I

Beta1,4-Galactosyltransferase I (GalT I) is localized on the leading lamellipodia of migrating cells, where it associates with the cytoskeleton and facilitates cell spreading and migration on basal lamina matrices. It has previously been reported that a variety of highly metastatic murine and human cell lines are characterized by elevated levels of cell surface GalT I, although the intracellular biosynthetic pool is similar between cells of high and low metastatic potential. In this study, we examined whether the elevated expression of surface GalT I characteristic of metastatic cells is instructive or incidental to their metastatic behavior by altering the expression of surface GalT I and by the use of GalT I-specific perturbants. Surface GalT I levels were positively and negatively altered on murine melanoma cells by either overexpressing full-length GalT I or by homologous recombination, respectively. The consequences of altered surface GalT I expression on cell invasion in vitro and lung colonization in vivo were determined. Increasing surface GalT I expression on cells of low metastatic potential to levels characteristic of highly metastatic cells recapitulated the highly invasive phenotype in vitro. Alternatively, decreasing surface GalT I expression on highly metastatic cells to levels characteristic of low metastatic cells reduced their invasive behavior in vitro and metastatic activity in vivo. Within the physiological range of surface GalT I expression, the invasive potential of each clonal cell line correlated strongly with the level of surface GalT I expressed. As an independent means to assess the involvement of surface GalT I in metastatic behavior, cells were pretreated with two different classes of surface GalT I perturbants, a competitive oligosaccharide substrate and a substrate modifier protein. Both perturbants inhibited metastatic colonization of the lung, whereas control reagents did not. Finally, as reported by others, surface GalT I on metastatic cells selectively interacted with one glycoprotein substrate, or ligand, of approximately 100 kDa, the identity of which remains obscure. These results show that the elevated expression of surface GalT I characteristic of highly metastatic cells contributes to their invasive phenotype in vitro and to their metastatic phenotype in vivo.

GENERATION OF ADP BY HUMAN AND MURINE TUMOR CELLS IS SPECIFIC BUT IS UNRELATED TO METASTATIC POTENTIAL

1987 ◽  
Author(s):  
G A Jamieson ◽  
G Grignani
Keyword(s):  
Tumor Cell ◽  
Metabolic Control ◽  
Tumor Cells ◽  
Cell Damage ◽  
Metastatic Potential ◽  
Iodoacetic Acid ◽  
Human Platelets ◽  
Significant Difference

The ability of tumor cells to activate platelets may facilitate the metastatic process. It has been generally assumed that the production of ADP by tumor cells is due to non-specific damage during harvesting in vitro or, in vivo, by frictional interactions with the capillary wall. The present work shows that tumor cell ADP arises not from cell damage but by a specific process under metabolic control. The human 253J urinary carcinoma cell line activated heparinized human platelets by an ADP-dependent mechanism based on inhibition by CP/CPK and the identification of aggregating concentrations (1 uM) of ADP in the cell-free supernatant by HPLC. Tumor cell damage during harvesting was shown not to be a factor since (i) the amount of ADP secreted was unrelated to the appearance of LDH, (ii) was similar when measured in confluent monolayers, in tumor cells after detachment and resuspension or following crossover studied in HBSS and MEM, and (iii) was constant at varying tumor cell concentrations. Metabolic control of ADP generation or transport was indicated by the fact that it was reduced 50 in tumor cells treated with p-chloromercuribenzene sulfonate and was completely abolished in those treated with iodoacetic acid. In order to determine whether this metabolically controlled generation of ADP was related to metastatic potential, we carried out identical experiments with the FI (low) and F10 (high) metastatic variants of the Bl6 murine melanoma line. The amounts of ADP produced by the B16 cells were about twice as great as with the human 253J cells but there was no significant difference between the amounts of ADP generated by FI and F10 variants. These studies demonstrate that ADP production by tumor cells is a discrete process under metabolic control but is not directly related to the metastatic potential of individual tumor cell lines.

Interaction between elastin and tumor cell lines with different metastatic potential; in vitro and in vivo studies

1991 ◽  
Vol 117 (3) ◽  
pp. 232-238 ◽  
Author(s):  
J. Timar ◽  
K. Lapis ◽  
T. Fulop ◽  
Z. S. Varga ◽  
J. M. Tixier ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cell Lines ◽  
Metastatic Potential ◽  
In Vivo Studies ◽  
Tumor Cell Lines

scholarly journals Cancer-Associated Mutations Reveal a Novel Role for EpCAM as an Inhibitor of Cathepsin-L and Tumor Cell Invasion

2020 ◽  
Author(s):  
Narendra Sankpal ◽  
Taylor C. Brown ◽  
Timothy P. Fleming ◽  
John M. Herndon ◽  
Anusha A. Amaravati ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Cancer Biology ◽  
Human Cancer ◽  
Cathepsin L ◽  
Surface Expression ◽  
Tumor Cell Invasion

Abstract BackgroundEpithelial cell adhesion molecule (EpCAM) is a 40-kD type-I transmembrane protein that is frequently overexpressed in human epithelial cancers. Recent evidence implicates EpCAM in the regulation of oncogenic signaling pathways and epithelial-mesenchymal transition. Of note, multiple proteins with thyroglobulin-type-1 (TY-1) domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor invasion and metastasis.MethodsHuman cancer sequencing studies reveal that somatic EpCAM mutations are present in up to 5.1% of tested tumors form public database search. To determine how EpCAM mutations affect cancer biology we studied C66Y, a damaging TY-1 domain mutation identified in liver cancer, as well as 13 other cancer-associated EpCAM mutations. Using in-vitro and in-vivo models, immunoprecipitations and localizations we demonstrate EpCAM inhibits CTSL activity based mutations and thereby its localization.ResultsWe demonstrate that wild type (WT) EpCAM, but not C66Y EpCAM, inhibits CTSL activity in vitro, and the TY-1 domain of EpCAM is responsible for this inhibition. WT EpCAM, but not C66Y EpCAM, inhibits tumor cell invasion in vitro and lung metastasis in vivo. In an extended panel of human cancer cell lines, EpCAM expression is inversely correlated with CTSL activity. Previous studies have demonstrated that EpCAM germline mutations can prevent EpCAM from being expressed at the cell surface. We demonstrate that C66Y and multiple other EpCAM cancer-associated mutations prevent surface expression of EpCAM. Cancer-associated mutations that prevent EpCAM cell surface expression abrogate the ability of EpCAM to inhibit CTSL activity and tumor cell invasion. ConclusionsThese studies reveal a novel role for EpCAM as a CTSL inhibitor, confirm the functional relevance of multiple cancer-associated EpCAM mutations, and suggest a therapeutic vulnerability in cancers harboring EpCAM mutations.

Procoagulant (Tissue Factor) Activity Is Higher In Cells From Murine Sarcoma Sublines With Lower Metastatic Potential

1981 ◽  
Author(s):  
M Colucci ◽  
R Giavazzi ◽  
G Alessandri ◽  
N Semeraro ◽  
A Mantovani ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Cancer Cell ◽  
Metastatic Potential ◽  
Procoagulant Activity ◽  
Autologous Plasma ◽  
Parent Line ◽  
Metastatic Capacity ◽  
Cell Invasiveness

It has been suggested that cancer cell procoagulant activity influences metastasis formation by promoting fibrin deposition around tumors. We have investigated the procoagulant activity of various tumor cell sublines with different metastatic capacity. These were derived from spontaneous lung nodules of mFS6, a benzopyrene-induced sarcoma in C57B1/6 mice. After one in vivo passage by s.c. implantation, the resulting tumor was cultured once in vitro till confluence; cells were then harvested from plastic bottles by trypsin treatment, and washed extensively after trypsin neutralization. Tumor cell procoagulant activity was measured by a one-stage clotting assay using autologous plasma. All the cells tested possessed thromboplastin-like activity since they shortened the recalcification time of normal and factor VUI-deficient plasma to a similar extent but had no activity on factor Vll-deficient plasma.They were, however, heterogeneous as regards the degree of procoagulant activity; the two cell lines with virtually no metastatic capacity showed 6-8 times higher procoagulant activity than the cells from the parent line; in contrast, the procoagulant activity of the two sublines with higher metastatic capacity did not differ significantly from that of the parent line.These findings support the hypothesis that fibrin is part of a defence reaction against cancer cell invasiveness.

Soluble syndecan-1 promotes growth of myeloma tumors in vivo

Blood ◽  
2002 ◽  
Vol 100 (2) ◽  
pp. 610-617 ◽  
Author(s):  
Yang Yang ◽  
Shmuel Yaccoby ◽  
Wei Liu ◽  
J. Kevin Langford ◽  
Carla Y. Pumphrey ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Poor Prognosis ◽  
Lymphoid Cells ◽  
Soluble Form ◽  
Collagen Gels ◽  
Transfected Cells ◽  
Immunodeficient Mice

Abstract Syndecan-1 (CD138) is a transmembrane heparan sulfate–bearing proteoglycan expressed by most myeloma plasma cells that regulates adhesion, migration, and growth factor activity. In patients with myeloma, shed syndecan-1 accumulates in the bone marrow, and high levels of syndecan-1 in the serum are an indicator of poor prognosis. To test the effect of soluble syndecan-1 on tumor cell growth and dissemination, ARH-77 B-lymphoid cells were engineered to produce a soluble form of syndecan-1. Controls included vector only (neo)–transfected cells and cells transfected with full-length syndecan-1 complementary DNA that codes for the cell surface form of syndecan-1. Assays reveal that all 3 transfectants have similar growth rates in vitro, but cells expressing soluble syndecan-1 are hyperinvasive in collagen gels relative to controls. When injected into the marrow of human bones that were implanted in severe combined immunodeficient mice, tumors formed by cells expressing soluble syndecan-1 grow faster than tumors formed by neo-transfected cells or by cells expressing cell surface syndecan-1. In addition, cells bearing cell surface syndecan-1 exhibit a diminished capacity to establish tumors within the mice as compared with both neo- and soluble syndecan-1–transfected cells. Tumor cell dissemination to a contralateral human bone is detected significantly more often in the tumors producing soluble syndecan-1 than in controls. Thus, high levels of soluble syndecan-1 present in patients with myeloma may contribute directly to the growth and dissemination of the malignant cells and thus to poor prognosis.

scholarly journals Cancer-associated mutations reveal a novel role for EpCAM as an inhibitor of cathepsin-L and tumor cell invasion

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Narendra V. Sankpal ◽  
Taylor C. Brown ◽  
Timothy P. Fleming ◽  
John M. Herndon ◽  
Anusha A. Amaravati ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Human Cancer ◽  
Cathepsin L ◽  
Surface Expression ◽  
Tumor Cell Invasion ◽  
In Vivo Models

Abstract Background EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors. Methods The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of cancer associated EpCAM mutations. To determine how EpCAM mutations affect cancer biology we studied C66Y, a damaging TY-1 domain mutation identified in liver cancer, as well as 13 other cancer-associated EpCAM mutations. In vitro and in vivo models were used to determine the effect of wild type (WT) and mutant EpCAM on CTSL activity and invasion. Immunoprecipitation and localization studies tested EpCAM and CTSL protein binding and determined compartmental expression patterns of EpCAM mutants. Results We demonstrate that WT EpCAM, but not C66Y EpCAM, inhibits CTSL activity in vitro, and the TY-1 domain of EpCAM is responsible for this inhibition. WT EpCAM, but not C66Y EpCAM, inhibits tumor cell invasion in vitro and lung metastases in vivo. In an extended panel of human cancer cell lines, EpCAM expression is inversely correlated with CTSL activity. Previous studies have demonstrated that EpCAM germline mutations can prevent EpCAM from being expressed at the cell surface. We demonstrate that C66Y and multiple other EpCAM cancer-associated mutations prevent surface expression of EpCAM. Cancer-associated mutations that prevent EpCAM cell surface expression abrogate the ability of EpCAM to inhibit CTSL activity and tumor cell invasion. Conclusions These studies reveal a novel role for EpCAM as a CTSL inhibitor, confirm the functional relevance of multiple cancer-associated EpCAM mutations, and suggest a therapeutic vulnerability in cancers harboring EpCAM mutations.

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Sign in / Sign up

Export Citation Format

Share Document