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)

Twenty-three cases (12 low grade, 11 high grade) of endometrial stromal sarcoma were studied with monoclonal antibodies to vimentin, keratin, desmin, muscle actin, epithelial membrane antigen, and collagen type IV, using the avidin-biotin immunoperoxidase method. Tumors were highly variable in the expression of these antigens. Some tumors contained both epithelial and smooth muscle-related antigens; others were immunoreactive only for the intermediate filament vimentin. Immunoreactivity patterns for metastases or recurrences were similar to the respective primary tumor and no correlation was observed between tumor grade and antigen expression. Normal myometrium, when present, was keratin-positive and variably epithelial membrane antigen-positive. We conclude that endometrial stromal sarcoma, as well as normal myometrium, may express both epithelial and/or muscle-related antigens. These findings most likely reflect a common mesodermal-mullerian derivation and illustrate the intimate relationship of the endometrial stromal cell to the endometrial glands and myometrium. Knowledge of these immunoreactivity patterns is essential when evaluating poorly differentiated uterine tumors or spindle cell tumors presenting in extrauterine locations.
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PMID:Immunohistochemistry of endometrial stromal sarcoma. 170 3

Myeloma behaves differently to other osteolytic tumours which metastasize to bone, in that the latter usually provoke reactive bone formation in the host bone. A previous study showed that a myeloma cell line (GM1500) secreted an osteoblast-inhibiting factor(s). The present study was undertaken to determine whether other myeloma cells also secreted a factor(s) which inhibited both cell proliferation and DNA synthesis of osteoblast-like cells and whether the myeloma also affected the function of osteoblasts. The results showed that a second cell line (Karpas 707) as well as myeloma tissue taken from two patients had a similar effect. The myeloma cells did not affect total collagen or protein synthesis, and did not affect the overall degree of mineralization. A biphasic effect was seen on alkaline phosphatase activity. Thus, although the proliferation of the pre-osteoblast was affected, the synthetic functions of the osteoblasts were not.
Clin Exp Metastasis 1992 Jan
PMID:Myeloma affects both the growth and function of human osteoblast-like cells. 173 45

We have investigated the effect of the immunomodulator ubenimex (hereafter referred to as bestatin) on the enzymatic degradation of the extracellular matrix by human renal cell carcinoma SN12M cells during the invasive process. The invasion of SN12M cells into reconstituted basement membrane (Matrigel) was inhibited by the presence of bestatin in a concentration-dependent manner. However, bestatin did not have any effect on tumor cell adhesion and migration to the extracellular matrices which may be involved in tumor cell invasion. Bestatin inhibited the degradation of type IV collagen by tumor cells, but not by tumor-conditioned medium (TCM), in a concentration-dependent manner. We also found that bestatin inhibited hydrolysing activities towards substrates of aminopeptidases in SN12M cells. Since bestatin was found to inhibit aminopeptidase activity, the inhibition of tumor invasion by bestatin is likely to be associated with its action as an enzyme inhibitor. Bestatin only slightly inhibited tumor cell plasmin activity, which can lead to the conversion of the latent collagenase to the active form, but this slight effect was not significant. The zymography of TCM from SN12M cells showed that the treatment of tumor cells with bestatin resulted in the disappearance of the 68 kDa type IV collagenase-enzyme level (active form) and slight reduction of the 72 kDa type IV collagenase-enzyme level (latent form). These results indicated that bestatin may inhibit tumor cell invasion through a mechanism involving its inhibitory action on aminopeptidases in tumor cells, suggesting that the aminopeptidase may partly be associated with the conversion of a latent form of type IV procollagenase to an active form or the secretion of the collagenases from tumor cells.
Clin Exp Metastasis 1992 Jan
PMID:Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin). 173 47

Sera of 85 patients with benign soft tissue lesions or sarcomas of soft tissues were investigated for a collagen metabolite, the aminoterminal propeptide of type III procollagen (PIIINP). Patients were divided into three groups: benign soft tissue lesions (n = 39), localised (n = 29) and metastatic (n = 18) soft tissue sarcomas (STS). Values of PIIINP above the reference range were found in 15%, 28% and 50% of the respective groups. The difference in the concentration of PIIINP was statistically significant between the benign lesions and the localised sarcomas; P = 0.05, and between the benign lesions and the metastatic sarcomas; P less than 0.001. In localised sarcomas there was a correlation between PIIINP and bone-involvement (r = 0.61, P = 0.002) and in metastatic disease between PIIINP and liver metastases (r = 0.77, P less than 0.001). In localised sarcomas the overall survival for patients with a value of PIIINP above the reference range was significantly poorer (P = 0.03) than for patients with values within the reference range, even after stratification for the histological malignancy grade of the tumours (P = 0.04).
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PMID:Type III collagen metabolism in soft tissue sarcomas. 173 16

Twenty-six cases of malignant peripheral nerve sheath tumor with a predominant epithelioid pattern were studied to determine the range of its histologic patterns, immunophenotype, and biologic behavior. The tumor presented as an asymptomatic mass either in superficial (16 cases) or in deep soft tissue (10 cases) of the extremity. Characteristically, those in deep soft tissue were composed of vague nodules of varying cellularity made up of cords or strands of rounded epithelioid cells with prominent nucleoli. Those in superficial soft tissue were uninodular masses composed of tight clusters of cells showing cell-to-cell molding but possessing the same prominence of nuclei and mitotic activity as those in deep soft tissue. Several were associated with a preexisting benign nerve sheath tumor. A number of cases deviated from the above description, including cases that resembled a clear cell carcinoma, a malignant rhabdoid tumor, and a pleomorphic sarcoma. The majority of cases (80%) strongly expressed S-100 protein and neuron-specific enolase, but all lacked a melanoma-associated antigen (as defined by HMB-45) and cytokeratin. Stains for type IV collagen defined linear immunoreactivity around single cells and groups of cells. This pattern did not differ substantially from that of melanomas and therefore did not serve as a reliable discriminant. Follow-up information indicated a more favorable course for those in superficial soft tissue compared with those in deep sites. Two of 16 patients in the former group developed metastatic disease compared with three of 10 in the latter group. Tumors in superficial soft tissue may be eminently treatable and curable, depending on size.
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PMID:Epithelioid variant of malignant peripheral nerve sheath tumor (malignant epithelioid schwannoma). 174 81

The cell spreading ability of human lung cancer cells on collagen substrata was examined in comparison with normal human tracheal epithelial cells. Plastic dishes or multiwells were coated with type I, III or IV collagen gel at a concentrate of 200 micrograms/cm2. Ninety per cent of the normal cells were round on all collagens. Adenocarcinoma RERF-LC-MS and VMRC-LCD cell lines and squamous cell carcinoma VMRC-LCP cell line, which metastasize weakly after intrasplenic transplantation in nude mice, spread relatively poorly. Adenocarcinoma, A549 and SK-LU-1 and squamous cell carcinoma Calu-1 cell lines, which were highly metastatic to liver, spread well. Adenocarcinoma ABC-1 cell line, which is moderately metastatic to liver in nude mice, spread moderately. On type III collagen, three adenocarcinoma cell lines (A549, ABC-1 and VMRC-LCD) gradually started to contract after initial spreading and became round at 24 h. These results suggest that there may be a correlation between the degree of malignancy of human lung cancer cells and their spreading ability on collagen substrata, and that the cell spreading ability may be regulated by type III collagen in some lung cancer cells.
Clin Exp Metastasis
PMID:The spread of human lung cancer cells on collagens and its inhibition by type III collagen. 175 82

The rebuilt tumor model is a three dimensional mass of tumoral cells and angioma fusiform cells in collagen. Rebuilt tumors can give rise to "in vitro metastases" and these metastases depend on the presence of a neomatrix secreted in vitro by rebuilt tumor cells. This study defines the origin of the neomatrix and its role in "in vitro metastasis". Fusiform cells of angioma origin (AF3cells) were stimulated ten-fold by growing them in conditioned medium from a human melanoma cell line (MM2). The stimulated AF3 cells produced a dense neomatrix that was firmly attached to the culture flask. The AF3 cells were removed and MM2 cells were grown on this neomatrix. They gave rise to tumorous nodules very like the "in vitro metastases" produced by rebuilt tumors. The MM2 conditioned medium contained basic fibroblast growth factor, which could account for the angiogenetic activity of the tumoral cells. The fusiform cells of angioma origin that are stimulated by cancerous conditioned medium, are responsible for secretion of the neomatrix which plays a role in "in vitro metastasis".
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PMID:Angioma fusiform cells stimulated by conditioned medium from melanoma cells secrete a neomatrix which plays a role in "in vitro metastasis". 177 23

Cells were seeded on top of a reconstituted collagen gel layer, and their migration into the gel was evaluated as an assay for invasive behavior. The method was standardized by measuring the depth of migration of each cell in a defined volume of the gel. We developed a microscope stage, controlled by a computer program. This semiautomatic counting method allowed precise vertical localization of each cell in a collagen gel with an error of less than 0.1 micron. To test the discriminative power of the assay, we used cell lines which were known to be invasive or noninvasive in other assays. Closely related variants of 2 cell families were chosen: (1) one family derived from a mouse mammary gland (NMuMG), and (2) one derived from a mouse T cell lymphoma (BW5147). The assay could discriminate between invasive and noninvasive variants of related cell lines within the same family. The profile of the number of cells in each layer of the gel provided additional discrimination between the different cell lines. Furthermore, the assay allowed direct microscopic observation of cells migrating in the collagen gel. The present standardization makes the collagen assay suitable for semiautomatic testing of the invasive phenotypes in cell populations from the same as well as from different cell families.
Invasion Metastasis 1991
PMID:Numerical evaluation of the invasion of closely related cell lines into collagen type I gels. 180 Apr 49

The development of the basal lamina (BL), the key structure of the basement membrane (BM), was investigated in three xenografted human carcinomas of the sigmoid colon (CA 1), the lung (L 261), and the hypopharynx (H-Stg 1) following heterotransplantation to athymic mice. The study involved the use of electron microscopy and indirect immunofluorescence techniques employing highly specific antibodies against the intrinsic BL components, heparan sulfate proteoglycan, laminin and type-IV collagen. Following transplantation, the extracellular matrix material of the transplanted tumors decomposed and was phagocytozed by invading macrophages within 1 to 2 days. During this stage, no specific binding of the applied antibodies to BL components could be detected within the xenografts. Following the ingrowth of host-derived connective tissue between days 2 to 6, small fluorescence-positive granules appeared within the cytoplasm and around those tumor cells that were located close to the invaded strands of connective tissue. Ultrastructurally, typical secretory granules were detectable in the cytoplasm of many xenografted carcinoma cells. Thereafter, a tannic acid-positive, patchy material appeared in the extracellular space of CA 1 and L 261 and aggregated to form small fragments of a discontinuous BL. In the H-Stg 1 xenografts, this material assembled to form continuous mono-, bi- and multi-layered structures. Large amounts of excess BL material remained accumulated in the L 261 and H-Stg 1 xenografts until the end of the observation period (day 24). These findings reveal that discontinuities of the BL occur independent of the active invasion processes of tumor cells, since xenografted human carcinomas neither grow invasively nor metastasize in nude mice. Moreover, they confirm that these discontinuities are not caused by a quantitatively insufficient production of BL material, but rather arise from qualitative imbalances of the composition of the synthesized BL material.
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PMID:Development of the basal lamina in xenografted human carcinomas: an ultrastructural and immunohistochemical study. 181 85

Medulloblastoma, a highly malignant pediatric tumor of the posterior fossa, demonstrates a marked propensity for leptomeningeal dissemination. Although the predominant site of relapse is the posterior fossa, the prevention of subarachnoid spread would be of significant therapeutic value. The established medulloblastoma cell lines D283 Med, D341 Med, D384 Med, D425 Med, D458 Med and Daoy have been investigated in in vitro adhesion assays for their capacity to bind to the predominant components of the leptomeningeal extracellular matrix: fibronectin, laminin and collagen IV. Growth on the reconstituted basement membrane matrix, Matrigel, was also assayed. Of the five neuronal phenotype DMed lines, all of which grow spontaneously as macrospheroids in standard fetal calf serum-containing tissue culture medium, only D425 Med and its sibline, D458 Med, derived from a subsequent sample from the same patient, displayed adherence to any of the substrata: approximately 20% of input D425 Med cells attached and exhibited cell spread and some extension (adhesion) on fibronectin. All other DMed lines failed to attach to these substrates. The glial phenotype cell line Daoy, which grows as an adherent monolayer under normal culture conditions, exhibited attachment, extension and growth on all substrata as did the glioma cell line U-251 MG and the neuroblastoma cell line SK-N-SH. The lack of attachment, and thus spread on components of the leptomeningeal extracellular matrix under in vitro assay conditions by 5/6 of the medulloblastoma cell lines investigated, is characteristic of neuronally differentiated cells, thus reinforcing the previously described neuronal phenotype of these lines. The readily demonstrated expression of N-CAM and L1 by all of the medulloblastoma cell lines suggests that the primary mode of leptomeningeal extension in vivo may be dependent on such other cell-cell and cell-substrate binding mechanisms.
Invasion Metastasis 1991
PMID:Medulloblastoma cell-substrate interaction in vitro. 182 45


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