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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first step in tumor metastasis is the detachment of cells from the primary tumor. If metastatic tumor cells have decreased levels of active homotypic cell adhesion molecules (CAMs), this might aid their escape from the primary tumor. In order to determine whether homotypic CAM activity might be reduced in metastatic cells, a new direct CAM assay was developed. The assay gave a linear response with respect to the concentration of a CAM fragment preparation from Balb/3T3 cells and was able to follow partial purifications of the CAM activity. The yield of homotypic CAM activity was measured from metastatic cells, related tumorigenic but nonmetastatic cells, and parental cells. The parental Balb/3T3 and nonmetastatic Balb/3T3 MSV85 cells yielded 22.5 +/- 1.1 (SD) and 24.8 +/- 3.5 units of CAM activity per mg of protein, whereas the metastatic Balb/3T3 K234 cells yielded only 4.6 +/- 0.8 units/mg. The homotypic adhesiveness of each of the cell lines was closely correlated with the level of CAM activity. When the CAM activity from each of the three cell lines was serially fractionated with the same column, the parental Balb/3T3 and nonmetastatic Balb/3T3 MSV85 cells each had one major peak of CAM activity that eluted in the same place. However, the metastatic Balb/3T3 K234 cells were missing this peak of CAM activity. These results suggest that levels of homotypic CAM activity are greatly reduced in a metastatic cell line because the cells are missing a specific CAM activity. This would presumably allow the metastatic cells to escape more easily from the primary tumor and provide a molecular explanation for how they can complete the first step in metastasis.
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PMID:A metastatic tumor cell line has greatly reduced levels of a specific homotypic cell adhesion molecule activity. 154 Sep 64

Adhesive interactions between lymphocyte cell-surface receptors and components of the vascular endothelium and the extracellular matrix play an important role in the control of lymphocyte migration and homing. To investigate whether lymphocyte adhesion molecules involved in the migration of normal lymphocytes, i.e., CD44 homing receptor, LFA-1 (CD11a/18), and ICAM-1 (CD54), also play a role in the spread and hence in the disease course of non-Hodgkin's lymphomas (NHL), expression of these molecules was examined in 78 cases of diffuse large-cell lymphoma. Other potential risk factors considered in this study were sex, age, primary tumor localization, lineage (T cell vs. B cell), and histopathological subtype. 27 of 53 (51%) patients with a lymphoma having a high CD44 antigen expression showed tumor spread beyond stage II at diagnosis while this was the case in only three of 25 (12%) patients with lymphomas that were CD44 low/negative (chi-square 25.4, p less than 0.001). Similarly, poor response to treatment, i.e., absence of remission or relapse, and or death from lymphoma, was more common among patients with lymphomas expressing high levels of CD44; actuarial survival among patients with CD44 high and low lymphomas was 47% and 91%, respectively (Mantel-Cox 6.1, p = 0.02). Neither LFA-1 nor ICAM-1 expression showed a significant correlation to lymphoma dissemination or disease course. Of the other factors considered, T cell phenotype was associated with an unfavorable prognosis while nodal localization was a risk factor for dissemination. Taken together, our findings suggest that CD44 antigen expression plays an important role in the dissemination of NHL and via this mechanism exerts an unfavorable prognostic influence.
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PMID:Adhesion molecules in the prognosis of diffuse large-cell lymphoma: expression of a lymphocyte homing receptor (CD44), LFA-1 (CD11a/18), and ICAM-1 (CD54). 197 38

CD44, an integral membrane glycoprotein expressed by many cell types, serves as the principal transmembrane hyaluronate receptor and may be a determinant of metastatic and invasive behavior in carcinomas. The expression of CD44 in 23 gastric adenocarcinoma and 12 peptic ulcer disease (PUD) resection specimens and gastric carcinoma cell lines HS746t and KATO III was examined by immunohistochemistry using the murine monoclonal antibody A3D8 on formalin-fixed, paraffin-embedded tissue or cells. Western blot analysis of whole cell lysates of KATO III and HS746t cells showed protein bands at 85 to 90 kd with KATO III cells expressing an additional band at 145 kd. In normal stomach gastric epithelium was negative. In PUD foveolar epithelium was focally positive, but staining did not correlate with the extent of gastritis. In carcinoma cases intensity of staining was progressively stronger comparing intestinal metaplasia with dysplasia with intramucosal carcinoma. Invasive carcinoma was invariably more strongly positive than dysplasia or intramucosal carcinoma. Twelve adenocarcinomas were weakly positive and 11 were strongly positive. The staining intensity of metastases (12 cases) was the same or weaker than the primary tumor. For the 12 patients whose carcinomas were weakly positive, mean length of survival for the six who died was 23.3 months. Five of the 11 patients whose carcinomas strongly expressed CD44 died within the study period with a mean length of survival of 11.0 months. A key consequence of CD44 overexpression in gastric carcinomas may be development of the invasive phenotype and strong expression may indicate a poorer prognosis.
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PMID:Expression of the cell adhesion molecule CD44 in gastric adenocarcinomas. 752 75

Squamous carcinomas of both human and rodent origin can undergo a transition to a more invasive, metastatic phenotype involving reorganization of the cytoskeleton, loss of cell adhesion molecules such as E-cadherin and acquisition of a fibroblastoid or spindle cell morphology. We have developed a series of cell lines from mouse skin tumors which represent different stages of carcinogenesis, including benign papillomas, and clonally related squamous and spindle carcinomas derived from the same primary tumor. Some spindle cells continue to express keratins, but with a poorly organized keratin filament network, whereas in others no keratin expression is detectable. All of the spindle cells lack expression of the cell adhesion molecule E-cadherin and the desmosomal component desmoplakin. Loss of these cell surface proteins therefore appears to precede the destabilization of the keratin network. At the genetic level, it is not known whether such changes involve activation of dominantly acting oncogenes or loss of a suppressor function which controls epithelial differentiation. To examine this question, we have carried out a series of fusion experiments between a highly malignant mouse skin spindle cell carcinoma and cell lines derived from premalignant or malignant mouse skin tumors, including both squamous and spindle carcinoma variants. The results show that the spindle cell phenotype as determined by cell morphology and lack of expression of keratin, E-cadherin, and desmoplakin proteins, is recessive in all hybrids with squamous cells. The hybrids expressed all of these differentiation markers, and showed suppression of tumorigenicity to a variable level dependent upon the tumorigenic properties of the less malignant fusion partner. Our results suggest that acquisition of the spindle cell phenotype involves functional loss of a gene(s) which controls epithelial differentiation.
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PMID:The conversion of mouse skin squamous cell carcinomas to spindle cell carcinomas is a recessive event. 768 80

The cell adhesion molecule (CAM) L1 is involved in homotypic and heterotypic adhesion between neural cells. It has recently also been identified on leucocytes. We have investigated the expression of L1 on hematopoietic tumor cell lines and found that several tumors including the ESb-MP lymphoma are positive for L1. A potential role for L1 in spontaneous metastasis formation was examined using these cells. From wild-type (wt) L1high lymphoma cells we selected by a fluorescence-activated cell sorter (FACS) stable L1low expression variants. Syngeneic DBA/2 mice injected subcutaneously with L1low clones showed faster primary tumor growth, developed visceral metastases significantly faster and died earlier than animals carrying L1high wt cells. L1 high revertants from the L1low variants showed again a reduced metastatic capacity and a malignancy similar to the wt cells. Expression of L1 on the tumor variants and revertants correlated directly with their homotypic aggregation behaviour in vitro. L1 expression correlated negatively with metastatic capacity. These results suggest that L1 molecules may contribute to the overall malignant potential of the lymphoma cells, presumably by interfering with cell-cell interactions critical for tumor growth and dissemination.
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PMID:Expression of L1 cell adhesion molecule is associated with lymphoma growth and metastasis. 837 17

It is now clear that adhesive interactions play a critical role in the process of metastatic tumor dissemination. Adhesion molecules act as both positive and negative modulators of the metastatic process. Molecules such as E-cadherin that promote homotypic tumor cell adhesion function to maintain intercellular contacts that confine cells to the primary tumor site and are negatively correlated with metastatic potential. Because tumor cells are rapidly eliminated from the circulation, those cells that can quickly arrest in the vasculature at a secondary site and pass through the vessel wall into the surrounding tissue will have a selective advantage toward establishing new metastatic colonies. The first step in this process is specific adhesion to venular endothelial cells in selected organs, a process mediated by tumor cell surface molecules such as Sialyl LewisX or the VLA-4 (alpha 4 beta 1) integrin that mediate binding to endothelial adhesion molecules such as the E-selectin or the vascular cell adhesion molecule, VCAM-1. Site-specific endothelial determinants such as the lung endothelial cell adhesion molecule, LuECAM, may additionally specify particular sites for preferential adhesion and subsequent site-specific metastasis of particular tumor types. After adherence to endothelial cells and subsequent endothelial retraction, metastatic tumor cells must adhere to elements of the subendothelial basement membrane such as laminin and types IV and V collagen, interactions frequently mediated by members of the beta 1 and beta 4 integrin families. Finally, metastatic tumor cell adhesion to connective tissue elements such as fibronectin, type I collagen and hyaluronan, mediated by molecules such as the beta 1 integrins and by the CD44 cell surface adhesion molecule, are required for movement of tumor cells into the subendothelial stroma and subsequent growth at these new sites. Thus, metastatic potential can be influenced both positively and negatively by a variety of cell surface adhesive molecules that act both independently and in concert to direct tumor cells to particular tissues, allowing them to arrest in those tissues, migrate across the vessel wall and grow at the secondary site. In the current review, I discuss the nature of the adhesion molecules that have been implicated in the metastatic process, emphasizing those molecules that have been shown to correlate with metastasis in clinical human tumors or that have been shown to influence metastatic potential in in vivo experimental assays.
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PMID:Adhesion molecules in tumor metastasis. 840 Jan 43

The cell-cell adhesion molecule E-cadherin has been shown to suppress invasive growth of epithelial cells in vitro, and loss of its expression is thought to be important in invasion and metastatic potential of epithelial tumors in vivo. We retrospectively studied the level of E-cadherin expression in 50 primary head and neck squamous-cell carcinomas (HNSCC) by immunohistochemical methods, on frozen sections, using anti-E-cadherin monoclonal antibody (MAb) 6F9. It concerned patients with different stages of carcinoma of larynx or oral cavity who had been treated with curative intention 30 months or more before. Percentages of membranous stained tumor cells were scored in 1 of 5 categories. Scores were generally low, as in 11/50 lesions < or = 5% cells were stained, and in 19/50 lesions only 6-25% cells showed membranous staining. In 9 lymph-node metastases evaluated, E-cadherin expression was in the same range as in the primary tumors. There was a significant correlation between the level of membranous E-cadherin expression in the primary tumor and the degree of differentiation. No relation was found with tumor size (pT) or regional lymph-node classification (pN). Nevertheless, 29 patients surviving > or = 30 months without evidence of disease had significantly higher levels of membranous E-cadherin expression in their primary tumors than 10 patients with unfavorable clinical course clearly related to recurrent and/or metastatic HNSCC. Moreover, this could only partially be explained by distinctions in differentiation grade between both groups. Our results suggest that membranous E-cadherin expression has prognostic importance in patients with HNSCC.
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PMID:E-cadherin expression in head and neck squamous-cell carcinoma is associated with clinical outcome. 840 85

Recently, we demonstrated that an immunoglobulin-like cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer. It is known that C-CAM is expressed in many epithelial cell types. In this study, we tested the possibility that C-CAM may also suppress bladder cancer progression. We used an orthotopic tumor model, which provides a relevant organ condition for examining the interaction between primary tumor cells and their microenvironment; this interaction has a critical impact on the behavior of carcinoma. We constructed a recombinant adenovirus expressing C-CAM1 (an isoform of C-CAM) and infected the 253J B-V cell line, a tumorigenic human bladder carcinoma subline. In vitro, C-CAM1 protein was detected in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. When these cells were injected orthotopically in nude mice, we found that the increased expression of C-CAM1 in the 253J B-V cells repressed the growth of 253J B-V-induced tumors. Taken together, these data indicate that C-CAM1 is a potent tumor suppressor in human bladder cancer.
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PMID:Suppression of human bladder cancer growth by increased expression of C-CAM1 gene in an orthotopic model. 875 7

Progression of malignant potential in ovarian cancer was investigated by comparing recurrent tumor with their primary tumor counterparts in terms of p53 and CD44 variant 6 (CD44v6) expression. Forty-three paired primary and recurrent tumors were immunohistochemically evaluated for expression of p53 and CD44v6. A paired analysis revealed that p53 and CD44v6 expression were significantly greater in recurrent tumors than those in the primary counterparts with statistical significance, respectively (P=0.0055 and 0.0071; Wilcoxon signed-rank test). No relationship between these two proteins was found. These results suggested that recurrent ovarian cancer may possibly express a stronger malignant potential in comparison to the primary tumor.
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PMID:Comparison of p53 and CD44 variant 6 expression between paired primary and recurrent ovarian cancer: an immunohistochemical analysis. 986 9

The outcome of breast carcinoma is usually determined by multiple factors. Aberrant expression of the cell adhesion molecule CD 44 has been claimed to be associated with poor prognosis in various human malignancies. This study was designed to investigate any correlation between the soluble adhesion molecule CD 44 and the clinicopathologic variables and to evaluate the possible prognostic significance of soluble CD 44. Venous blood samples were preoperatively collected from 100 patients with invasive breast carcinoma. The serum levels of different soluble CD 44 molecules (CD 44 standard form and CD 44 splice variant V6) were measured with an enzyme immunoassay method. The data of primary tumor status, age, estrogen receptor status, lymph node status, histologic grading, distant metastases status, TNM staging, S-phase fraction, and ploidy pattern were collected and evaluated simultaneously with the serum levels of soluble CD 44 st and CD 44 V6. Twenty healthy subjects were used as the control group. The serum levels of soluble CD 44 st showed no significant elevation in patient group. The mean value of soluble CD 44 V6 in patient group was 269.2 +/- 94.3 ng/ml and that of the control group was 179.5 +/- 50.7 ng/ml; the difference was significant (p < 0.01). In multivariate analysis, distant metastasis (p < 0.05) and TNM staging (p < 0.01) appeared as independent factors regarding the significant higher serum levels of soluble CD 44 V6. Based on our preliminary results, preoperative serum soluble CD 44 V6 is closely related to distant metastases and TNM staging. The possible role of soluble CD 44 V6 in the prognostic value of breast carcinoma deserves further elucidation and evaluation with long-term patient follow-up.
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PMID:Evaluation of the prognostic value of serum soluble CD 44 in patients with breast cancer. 1059 65


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