Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggest that expression of CD44 splice variants are of prognostic significance for a variety of neoplasias. It was the aim of this study to investigate whether any correlation exists between the concentration of soluble CD44 molecules in serum (CD44 standard form and CD44 splice variants v5 and v6) and the prostate cancer stage. Serum levels of these soluble CD44 isoforms were measured by ELISA tests specific for these proteins in controls (n = 30), patients with benign prostatic hyperplasia (BPH; n = 30), with prostate cancer without metastasis (T1,2,3pN0M0; n = 30) and with locally advanced prostate cancer and/or metastatic disease (T3,4pN1,2M1; n = 19). sCD44std and sCD44v6 concentrations were not significantly different among the four groups studied, with few patients' levels outside the central 95% reference intervals. The mean sCD44v5 concentrations of both prostate cancer and BPH patients were significantly lower than those of the controls. There was no significant difference between the soluble CD44 concentrations of the two groups of prostate cancer patients studied. In contrast to results observed in other carcinomas, the determination of soluble CD44 proteins in serum is not suitable for providing additional prognostic information on patients with prostate cancer.
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PMID:Soluble CD44 molecules in serum of patients with prostate cancer and benign prostatic hyperplasia. 869 65

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.
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PMID:Induction of apoptosis of metastatic mammary carcinoma cells in vivo by disruption of tumor cell surface CD44 function. 939 67

Primary breast cancers were shown to overexpress CD44 v5 and v6 at the plasma membrane. However, the clinical significance of this overexpression remains unclear. Overexpression of CD44 v5 and v6 in primary breast cancers was found to correlate with metastasis and poor prognosis by some investigators, yet this correlation could not be confirmed by others using different antibodies. In this study the influence of metastatic disease, the site of metastasis, and the amount of CD44 v5 and v6 expression in the primary tumor on serum levels of the soluble forms of CD44 v5 and v6 (sCD44 v5 and v6) in breast cancer patients was investigated. Soluble CD44 v5 and v6 serum levels were measured by enzyme linked immuno sorbent assay in a group of breast cancer patients who developed metastases in various organs and in another group of patients with single organ metastasis. For control, sCD44 v5 and v6 levels were measured in breast cancer patients who remained free of metastasis and in healthy blood donors. Expression of plasma membrane bound CD44 v5 and v6 in the primary tumors of the patients with metastasis in various organs was correlated to sCD44 v5 and v6 levels in serum. Furthermore the size of sCD44 v6 was analyzed by immunoblot using a monoclonal antibody directed against CD44 v6. When metastases were detected, sCD44 v5 and v6 serum levels were increased as compared to levels measured one month after tumor surgery in patients free of metastases (p= 0.0025 and p=0.0004). Six of 19 and 6 of 20 patients had sCD44 v5 and v6 serum levels above a cut-off level of 85 and 275 ng/mL, respectively. In these cases expression of CD44 v5 and v6 in the primary cancers was also elevated. Low sCD44 v5 and v6 serum levels were associated with weak expression of CD44 v5 and v6 in the respective primary cancers. As shown by statistical analysis of sCD44 v5 and v6 levels in 57 patients with single organ metastases, elevated sCD44 v6 levels but not sCD44 v5 levels were associated with metastases in liver or bone (p=0.0025). Immunoblot analysis of soluble CD44 proteins in serum revealed two CD44 v6 specific signals of approximately 120 and 170 kDa. Increased sCD44 v5 and v6 serum levels in patients with breast cancer were influenced by the amount of CD44 v5 and v6 expression in the primary tumor by the site of metastasis. Elevated sCD44 v6 serum levels were preferentially found in patients with metastases in liver or bone.
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PMID:Soluble CD44 v5 and v6 in serum of patients with breast cancer. Correlation with expression of CD44 v5 and v6 variants in primary tumors and location of distant metastasis. 949 73

Aberrant expression of CD44 splice variants has been detected on a variety of human tumor cells. Overexpression of specific isoforms has been shown to be associated with metastasis and poor prognosis in breast cancer. We evaluated the possible utility of soluble CD44 splice variant v5 (sCD44v5) as a circulating, tumor-associated marker in breast cancer patients. Serum levels of sCD44v5 were determined in 147 healthy volunteers, in 53 patients with nonmalignant breast disease, in 85 patients with breast cancer at presentation, in 13 patients with recurrence and in 73 patients with active metastatic disease. Statistically, the levels at presentation in stages I-IV, in benign disease, and in a female control group were not significantly different. First longitudinal studies over 1-2 years in the follow-up of 28 patients who have remained tumor-free showed considerable between-patient variation while the intrapatient levels remained within relatively narrow limits. In patients with active metastatic disease, elevated levels of sCD44v5 (> 58 ng.ml-1) were detected in 50% of the cases with marked elevation in only 26%. In these cases, sCD44v5 correlated with the extent of metastatic disease and fell during clinical response to cytoreductive therapy. In comparison with CA15-3 in the patients' follow-up serum levels of sCD44v5 proved to be much less sensitive concerning lead time, percentage of raised serum levels at the time of recurrence and in metastatic disease. The value of sCD44v5 determinations in breast cancer patients was further limited by the poor diagnostic specificity of this marker due to elevated levels in smokers and chronic inflammatory disease.
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PMID:Evaluation of soluble CD44 splice variant v5 in the diagnosis and follow-up in breast cancer patients. 952 62

CD44 is a transmembrane glycoprotein involved in cell-cell and cell-substrate interactions. As a cell surface molecule, CD44 may be shed or released into the circulation by proteolytic enzymatic mechanisms. Therefore, soluble CD44 can be found in cell culture supernatants as well as in plasma. In this study we evaluated the levels of soluble total CD44 (sCD44) in serum samples of patients with breast and colorectal carcinoma as well as non-Hodgkin's lymphoma in order to correlate prognosis with sCD44 expression. Besides, we evaluated other clinical tumour markers routinely used, Cancer Antigen (CA) 15.3 and CA 19.9. We investigated 132 serological samples from breast cancer patients, 48 sera from colorectal tumours, 48 samples from stage IV non-Hodgkin's lymphoma and sera from 80 individuals without evidence of cancer or autoimmune disease. Breast cancer patients were divided into three groups: a) patients with no clinical evidence of positive nodules and no metastatic disease; b) patients with positive nodules; and c) patients with metastasis. sCD44 mean serum levels in these groups were 198+/-54 ng/ml, 221+/-78 ng/ml and 242+/-119 ng/ml, respectively, while the marker CA 15.3 values were 15.6+/-6.6 U/ml, 14.0+/-5.8 U/ml and 211.5+/-358.9 U/ml, respectively. sCD44 levels for colorectal tumour were 243+/-72 ng/ml, while CA 19.9 serum levels were 230+/-270 U/ml. Stage IV non-Hodgkin's lymphoma sCD44 levels were 398+/-160 ng/ml. sCD44, CA 15.3 and CA 19.9 values for healthy individuals without evidence of any cancer pathology were 223+/-58 ng/ml, 16.4+/-6.2 U/ml and 33+/-14 U/ml, respectively. From these results we conclude that sCD44 might be used as a reliable marker for patients with non-Hodgkin's lymphoma. However, sCD44 levels failed to correlate with prognosis, tumour burden or metastasis in breast and colorectal cancer patients. Neither was any correlation found between high CA 15.3 or CA 19.9 levels and soluble CD44 serum level.
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PMID:Evaluation of soluble CD44 in patients with breast and colorectal carcinomas and non-Hodgkin's lymphoma. 1042 14

Concentrations of soluble CD44 standard (sCD44std) and CD44 variant 6 (sCD44v6) isoforms were determined in the sera of 59 patients with distant metastasis from breast cancer receiving second line hormone- or chemotherapy, in comparison to 46 breast cancer patients without detectable recurrent disease and 21 healthy blood donors. The sera of non-metastatic breast cancer, patients contained sCD44std and sCD44v6 concentrations similiar to those of healthy blood donors. In sera of patients with distant metastasis from recurrent breast cancer the median values of sCD44std and sCD44v6 were significantly higher (sCD44std: 502 ng/ml, p=0.03; sCD44v6: 193 ng/ml, p = 0.002) in comparison to healthy blood donors and patients with non-metastatic disease (p<0.001 for both parameters). A significant correlation was observed between sCD44v6 serum concentrations and the number of metastasized organs (p=0.0018), serum LDH concentrations (p<0.0001), tumor grading (p=0.025) and the presence of hepatic metastasis (p=0.028). Furthermore, sCD44v6 expression was associated with the patient's responsiveness to second line hormone- or chemotherapy. Non-responders had significantly higher sCD44v6 levels compared with the responder group (median: 447 ng/ml vs 171 ng/ml; p=0.0007). Logistic regression analysis indicated that sCD44v6 serum levels above 250 ng/ml (p =0.033) and the presence of hepatic metastasis (p=0.009) were independent factors predicting an unfavourable response to therapy.
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PMID:Predictive relevance of soluble CD44v6 serum levels for the responsiveness to second line hormone- or chemotherapy in patients with metastatic breast cancer. 1171

We have shown recently that the hyaluronan receptor, CD44, and matrix metalloproteinase 9 (MMP-9) form a complex on the surface of TA/St mouse mammary carcinoma cells that activates latent transforming growth factor-beta (TGF-beta) and is required for tumor invasion. Disruption of the CD44/MMP-9 complex by expression of soluble CD44 results in the loss of tumor invasiveness and abrogates tumor cell survival in host lung parenchyma following intravenous injection into syngeneic mice. To explore the molecular nature of the survival signals derived from the CD44/MMP-9 complex during the development of tumor metastasis, we investigated the possibility that activation of latent TGF-beta by the CD44/MMP-9 complex is responsible for tumor cell survival in host lung parenchyma. TA3 cells overexpressing dominant negative soluble CD44 (TA3sCD44), which compromises native CD44 function and the ability of TA3 cells to develop metastases, were transfected with constitutively active or latent TGF-beta2 and tested for their ability to form tumors in syngeneic mice. Our results demonstrate that expression of the constitutively active, but not the latent, form of TGF-beta2 rescues TA3sCD44 cells from apoptosis during lung colonization. These observations provide evidence that activation of latent TGF-beta constitutes an event downstream of CD44-dependent signals that is required for tumor cell survival and metastatic colony formation. The functional axis composed of CD44, MMP-9 and TGF-beta may therefore play an important role in the metastatic proclivity of selected tumor types.
Clin Exp Metastasis 2004
PMID:Transforming growth factor-beta facilitates breast carcinoma metastasis by promoting tumor cell survival. 1538 73

Immunohistochemical expression of standard and v6 isoforms of CD44 was performed on specimens from three groups of prostate cancer patients: Group I, primary prostate cancers (N=31); Group II? lymph node metastases (N=18); and Group III, bone metastases (N=15). In addition, serum from all Group I patients was analyzed for soluble CD44 expression. Benign glands exhibited strong CD44s and CD44v6 expression in basal cells. Weak basolateral staining was identified in superficial luminal cells. Malignant glands and metastatic tumors revealed diminished or absent expression of both CD44s and CD44vG with a heterogeneous pattern. Pretreatment with chondroitinase did not significantly alter CD44 expression. Soluble CD44 was present in all serum samples, however, expression was variable. There was no statistically significant correlation between immunohistochemical CD44 expression, soluble CD44 expression, and clinical progression.
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PMID:Immunohistochemical and soluble expression of CD44 in primary and metastatic human prostate cancers. 2153 33

CD44 is an adhesion molecule involved in tumor cell invasion and metastasis. The function of CD44 in breast cancer is not understood completely, or is its role as a predictive or prognostic factor. In this study, we tested for the hypothesis that the concentration of soluble CD44 (sCD44) in serum is correlated with clinicopathological factors, especially HER2, and survival in patients with breast cancer. We retrospectively identified 110 patients with breast cancer who had been treated at The University of Texas MD Anderson Cancer Center (MDACC) from September 2001 to May 2004. Sera were collected before definitive surgery in patients with stage I or II breast cancer, before initiation of neoadjuvant chemotherapy (if indicated) for patients with stage I-III breast cancer, and before initiation of systemic therapy in patients with stage IV breast cancer. sCD44 levels were determined using an enzyme-linked immunosorbent assay. The median age at diagnosis was 51 years (range, 28.6-87.1 years). sCD44 concentration was correlated with tumor stage (P = 0.0308). sCD44 serum concentration did not predict pathological response in patients treated with neoadjuvant chemotherapy. Among patients with distant metastases, sCD44 levels were significantly higher in patients with liver involvement than in patients with metastases at other sites. The overall survival rate did not differ between patients with high sCD44 concentration and patients with low sCD44 concentration. However, sCD44 concentration was a significant predictor of overall survival for patients with HER2-positive breast cancer, while no difference in overall survival rates was observed in patients with HER2-negative breast cancer. To the best of our knowledge, this is the first study to show an association between circulating sCD44 levels and survival in HER2-positive breast cancer patients. Our results suggest a role for sCD44 as a prognostic marker. Furthermore, sCD44 level may offer a new clinical therapeutic target in HER2-positive breast cancer.
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PMID:Serum CD44 levels and overall survival in patients with HER2-positive breast cancer. 2183 16

CD44 is a cell surface adhesion receptor that is highly expressed in many cancers and regulates metastasis via recruitment of CD44 to the cell surface. Its interaction with appropriate extracellular matrix ligands promotes the migration and invasion processes involved in metastases. It was originally identified as a receptor for hyaluronan or hyaluronic acid and later to several other ligands including, osteopontin (OPN), collagens, and matrix metalloproteinases. CD44 has also been identified as a marker for stem cells of several types. Beside standard CD44 (sCD44), variant (vCD44) isoforms of CD44 have been shown to be created by alternate splicing of the mRNA in several cancer. Addition of new exons into the extracellular domain near the transmembrane of sCD44 increases the tendency for expressing larger size vCD44 isoforms. Expression of certain vCD44 isoforms was linked with progression and metastasis of cancer cells as well as patient prognosis. The expression of CD44 isoforms can be correlated with tumor subtypes and be a marker of cancer stem cells. CD44 cleavage, shedding, and elevated levels of soluble CD44 in the serum of patients is a marker of tumor burden and metastasis in several cancers including colon and gastric cancer. Recent observations have shown that CD44 intracellular domain (CD44-ICD) is related to the metastatic potential of breast cancer cells. However, the underlying mechanisms need further elucidation.
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PMID:CD44: A Multifunctional Cell Surface Adhesion Receptor Is a Regulator of Progression and Metastasis of Cancer Cells. 2832 6


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