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)

Tumor H-59 is a variant of the Lewis lung carcinoma which is metastatic to the liver. In previous studies we have shown that liver metastasis in this tumor model correlates with adhesion in vitro to hepatocyte monolayers (Brodt, P., Clin. Exp. Metastasis, 7: 525-539, 1989). In an attempt to identify the adhesion molecule(s) involved, monoclonal antibodies were produced. One monoclonal antibody (MAb C-11) was highly specific to hepatocyte-adherent tumor cells. The antibody (an IgG1) and F(ab)2 fragments blocked tumor cell attachment to hepatocytes while having no effect on tumor cell adhesion to basement membrane proteins coated onto culture dishes. Western blot analysis of solubilized 11-59 plasma membranes or cell lysates showed that the antibody recognizes an Mr 64,000 protein. Treatment with N-glycosidase F prior to Western blot analysis revealed that N-linked carbohydrate residues constitute approximately 43% of the total weight of this molecule. This glycoprotein is only weakly expressed on tumor M-27, a lung-specific subline of the Lewis lung carcinoma (Brodt, P., Cancer Res., 46: 2442-2448, 1986), is undetectable in plasma membrane preparations obtained from spleen cells and thymocytes, but can be detected on cultured hepatocytes and in hepatocyte cell lysates. Pretreatment of the hepatocytes with MAb C-11 also resulted in inhibition of tumor cell adhesion. These results suggest that this glycoprotein mediates the attachment of H-59 cells to hepatocytes.
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PMID:Identification of an Mr 64,000 plasma membrane glycoprotein mediating adhesion of tumor H-59 cells to hepatocytes. 205 93

Sixteen patients with primary breast cancer were studied with a pancarcinoma monoclonal antibody B72.3, an IgG1 molecule directed against tumor-associated glycoprotein (TAG-72) present in several tumors. Five millicuries of 111In was used to label 0.2 mg (six patients), or 2 mg (six patients), or 20 mg using the site-directed bifunctional DTPA method (at carbohydrate moiety). Digital, planar, and SPECT images were obtained at 2, 48, 72 and 96 hr when possible. HAMA levels were obtained before the Mab infusion and at 1, 3, and 6 wk postinfusion. Fourteen of 14 known primary breast lesions were detected by imaging (100% sensitivity). Two fibrocystic lesions were negative. Seven of 14 patients had lymph node metastases by histologic methods, but all were missed by radioimmunoscintigraphy. Tumor uptake of Mab ranged 0.00054%-0.0038% of the ID/g. The tumor-to-normal breast tissue ratio was 4.3 +/- 0.91 (mean +/- s.e.m.). Lymph nodes localization of 111In-B72.3 by tissue analysis was similar for tumor-bearing and normal nodes (0.0039 +/- 0.0023 versus 0.0025 +/- 0.0019). Pharmacokinetics revealed mean plasma half-life of 33.3-41.2 hr for the different doses. There was no statistical difference between any of the pharmacokinetic parameters of different doses. HAMA was positive only in 17% of the patients. The study suggests that this antibody has 100% sensitivity for primary breast cancers, but very poor detection rate of metastatic lesions in axillary lymph nodes; thus making it of questionable value in the initial staging process of this disease.
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PMID:Indium-111-labeled B72.3 monoclonal antibody in the detection and staging of breast cancer: a phase I study. 206 85

Laminin, a major glycoprotein of basement membrane has been found to play significant roles during invasion and metastases. In this study, we have examined the distribution of laminin in several human brain carcinoma metastases, human breast cancers, skin and lymph node metastases of breast cancer as well as in an in vitro and an in vivo model of invasion. A laminin accumulation was demonstrated a) at the border between human metastatic carcinoma cells and surrounding neural tissue; b) at the invasive edge between MO4 cells (a highly malignant cell line which synthesizes large amounts of laminin) and host tissues of syngenic mice; c) at the front of invasion between MO4 cells and precultured heart fragments in an in vitro model of invasion. Laminin, but not type IV collagen, promoted attachment of MO4 cells. This attachment was inhibited by preincubation of laminin matrix support with (+)-catechin, a flavonoid which also prevented invasion of the precultured heart fragment in vitro. Our data demonstrate that laminin accumulates between malignant cells and host tissue in human brain metastases and in an in vitro and an in vivo model of invasion. In these later models, accumulation of laminin is the consequence, at least in part, of its biosynthesis by MO4 cells. Since laminin promotes attachment of malignant cells in vitro, increases invasiveness and metastatic activities of murine malignant cells, it is tempting to speculate that laminin synthesized by invasive cells and accumulated at the front of invasion plays a significant role in the first step of invasion.
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PMID:Absence of laminin deposition in breast cancer and metastases except to the brain. 206

Over the past several years, many tumor markers, including cell surface antigens, T-antigen, ras p55, and ras p52 proteins, have been studied as potential tumor markers of bladder cancer. The lack of specificity and inconsistency of these markers led us to develop a new method for studying the urinary excretion of autocrine motility factor (uAMF) and tumor cell collagenase stimulating factor (TCSF) in 24-hour and first morning voided specimens. AMF is a glycoprotein secreted by the malignant cells and is responsible for cell locomotion, a key event in invasion and metastases of the malignant cells. TCSF is a membrane bound glycoprotein of tumor cells that stimulates fibroblast collagenase production. We have utilized an enzyme-linked immunoabsorption assay to detect the levels of uAMF and TCSF in urine samples collected from normal volunteers, patients with benign diseases, and patients with bladder cancer. Our data indicate that urinary concentrations of uAMF and TCSF are elevated in patients with bladder cancer. Furthermore, the levels of uAMF and TCSF are more elevated in invasive tumors as compared with benign counterparts. We have localized uAMF and TCSF in bladder cancer cells, utilizing immunohistologic techniques.
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PMID:A new method for evaluation of urinary autocrine motility factor and tumor cell collagenase stimulating factor as markers for urinary tract cancers. 212 27

Serum CA 19-9 was determined in 83 control subjects, 99 patients with pancreatic cancer, 104 with chronic pancreatitis and 137 with extra-pancreatic diseases mainly of gastrointestinal origin in order to evaluate whether hepatic factors can influence circulating CA 19-9 in pancreatic cancer. Sensitivity, specificity and accuracy of this test in determining pancreatic malignancy were: 74%, 83% and 57%. We divided patients into two groups: group A (159 cases) and group B (181 cases) with and without anatomical liver damage (presence of primary or metastatic cancer, cirrhosis, hepatitis, steatofibrosis, cholangitis). Group A presented higher CA 19-9 values as compared to group B. Significant correlations were found in group B but not in group A between CA 19-9 and ALT, ALP and total bilirubin. Multiple regression analysis (CA 19-9 dependent and ALT, ALP and total bilirubin predictor variables) was significant only in group B. The standardized partial regression coefficients found to be significant were those of ALP and total bilirubin. We can conclude that CA 19-9 is an index of pancreatic cancer with satisfactory sensitivity and specificity. The presence of anatomical liver damage seems to increase the value of this index, probably releasing CA 19-9 into the bloodstream. Extra-hepatic cholestasis may also be an important factor in elevating CA 19-9 probably by reducing the hepatic catabolism of this glycoprotein.
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PMID:How does liver dysfunction influence serum CA 19-9 in pancreatic cancer? 213 20

Tumor cells attach, degrade, and migrate through basement membranes as they metastasize. Laminin, a major glycoprotein of basement membranes, promotes the metastatic activity of tumor cells by stimulating the attachment and migration of the cells and their secretion of collagenase IV. We have identified a synthetic peptide of 19 amino acids (Cys-Ser-Arg-Ala-Arg-Lys-Gln-Ala-Ala-Ser-Ile-Lys-Val-Ala-Val-Ser-Ala-Asp -Arg) from the sequence of the A chain of laminin that increases experimental metastases of the lungs by murine melanoma cells. The peptide is active when injected either intravenously or intraperitoneally. The peptide increased collagenase IV activity, a key enzyme in the breakdown of basement membranes, to the same extent as laminin. This peptide represents an active site on laminin for promotion of the metastatic phenotype and generates a probe for studying the regulation of malignant activities.
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PMID:Identification of an amino acid sequence from the laminin A chain that stimulates metastasis and collagenase IV production. 215 66

A monoclonal antibody 7A9 was raised against the tumour-associated glycoprotein TAG-12 purified from T47-D breast carcinoma cells. In immunoblots from cytosol of T47-D cells and from sera of breast cancer patients, antibody 7A9 detects the high molecular weight mucin-like TAG-12 antigen. A series of paraffin sections of normal, benign and malignant mammary tissues have been studied with monoclonal antibody 7A9 and the immunoalkaline phosphatase method. In resting gland, proliferating gland and fibroadenoma ducts, reactivity of 7A9 was mainly restricted to luminal membranes of epithelial cells and secretions. 77/79 primary breast carcinomas including ductal, lobular and various other carcinoma types showed cytoplasmic and/or membrane-associated staining with 7A9 in most tumour cells. Metastases (31/31) from different sites were also positive. Strong immunoreactivity with single tumour cells was noted in cytological preparations from freshly resected breast cancer tissue. Thus, monoclonal antibody 7A9 seems to be very useful for the targeting of breast carcinoma cells.
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PMID:Analysis of the tumour-associated antigen TAG-12 by monoclonal antibody 7A9 in normal, benign and malignant mammary tissues. 215 77

Type IV and interstitial collagenolytic activities were compared in human malignant and normal trophoblast cells cultured on plastic, in presence or absence of laminin in solution, on matrigel (a gel of basement membrane components) and on type I collagen gel. Laminin highly stimulated the type IV collagenolytic activity but not the interstitial collagenolytic activity, in malignant trophoblast cells. This glycoprotein had no effect on the interstitial collagenolytic activity and doubled the type IV collagenolytic activity in normal trophoblast cells. Thus malignant trophoblast cells produce preferentially the enzyme able to degrade basement membrane when in contact with laminin, and the enzyme able to degrade interstitial collagen fibers when cultured on type I collagen. On the contrary, type I collagen gel and matrigel equally increased both type IV and interstitial collagenolytic activities by normal trophoblast cells. Interactions of tumor trophoblast or normal trophoblast cells with the extracellular matrix result thus in distinct stimulations of collagenolytic activities. Increased production of type IV collagenolytic activity upon exposure to laminin appears to be specific of the metastatic phenotype.
Invasion Metastasis 1990
PMID:Type IV and interstitial collagenolytic activities in normal and malignant trophoblast cells are specifically regulated by the extracellular matrix. 215 47

1. Binding to and destruction of basement membrane (BM) are necessary steps for cancer cells to extravasate and metastasize. Serum levels of released BM components may correlate with the staging of human cancers or with inflammatory disorders. Furthermore, released material may also induce autoantibodies. Since laminin, an 800-kDa glycoprotein, is present in the extracellular matrix, serum laminin levels may be markers of BM injury. 2. A two-site enzyme immunoassay and a radioimmunoassay were developed to test sera from patients with breast cancer or systemic lupus erythematosus (SLE). 3. A significant difference in laminin concentrations was demonstrated between early (T0-T2) and advanced (T3-T4) tumors (P = 0.001). However, specimens from SLE patients did not differ in laminin concentration from normal individuals and no correlation was observed between laminin levels and anti-laminin auto-antibody titers. 4. These results suggest that serum laminin levels are useful markers of BM damage and could be of prognostic value in cancer.
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PMID:Two-site immunoassays for the measurement of serum laminin: correlation with breast cancer staging and presence of auto-antibodies. 220 42

Spontaneously occurring microscopic lung and lymph node metastases (in athymic mice) of a low metastatic human lung carcinoma cell line, UCP3, and its high metastatic variant, MV522, were isolated. Characterization of the variants included karyotypic and isoenzyme analyses; assessment of spontaneous metastatic capabilities in athymic mice, and monoclonal antibody analyses. The high metastatic variant LNT had barely detectable amounts of a glycoprotein molecule with apparent Mr 73 kd and 90 kd, which was present in the other cell lines. This molecule was detected in 20/24 primary human neoplasms but only in 3/18 metastatic neoplasms, suggesting a loss during the metastatic disease process.
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PMID:Spontaneously metastasizing variants of a human lung carcinoma cell line: monoclonal antibody characterization. 224 63


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