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)

Four mouse B16 melanoma subclones (G3.15, G3.5, G3.12 and G3.26) exhibit progressively greater growth capacity in vitro and in vivo. Previously, non-metastatic G3.15 cells were sequentially converted, in monolayer cultures, to the moderately-metastatic G3.5 cells, and then to a highly-metastatic G3.5* phenotype. Both conversions were induced by hypoxia followed by confluence, and also occurred in tumors. G3.5* cells were comparable with, yet distinguishable from, G3.12 cells in being growth-autonomous in culture. In this study, the presumption that rapidly-growing G3.26 cells represented the ultimate progression step in this clonal system was examined. Both G3.12 and G3.5* cells converted in vitro to the G3.26 phenotype during growth in serum-free medium conditioned by G3.26 cell growth. By selective filtration of conditioned medium and characterization of the stability of growth- and conversion-promoting activities, three distinct activities were found to promote a two-step G3.12 to G3.26 phenotype conversion: (1) a < 10 kDa filtrate stimulated slight attachment and proliferation of G3.12 cells, effects that were reversible, partly attributable to accumulated lactate, and fully mimicked by medium acidification to pH 6.5; (2) medium acidification, together with a heat- and acid-stable but partially trypsin-sensitive > 10 kDa activity, induced G3.12-->G3.5* conversion that resulted in acquisition of growth autonomy; and (3) a heat-, acid- and trypsin-sensitive > 10 kDa activity induced G3.5*-->G3.26 conversion, characterized by anchorage-independent growth in soft agar, and potent lung colonization following intravenous injection. Phenotype analysis of G3.12 tumors and lung metastases revealed that G3.5*-like cells were regularly present in tumors and metastases, whereas G3.26-like cells occurred almost exclusively in large lung metastases. While G3.12 cells might convert to G3.5* cells in order to disseminate, G3.26 cells are apparently not involved in metastatic spread but probably account for the rapid growth of established metastases.
Clin Exp Metastasis 1995 Mar
PMID:Malignant progression of B16 melanoma cells induced in vitro by growth factors produced by highly malignant cells. 788 13

Acinar cell carcinoma is a rare pancreatic neoplasm that may contain scattered endocrine cells in as many as 40% of cases. In addition, unusual tumors exist in which the acinar and endocrine components each constitute a significant proportion (> 25%) of the neoplasm; we propose to designate them as "mixed acinar-endocrine carcinomas." In a study of five such cases, we found one case with segregated areas of acinar and endocrine cells that were identifiable in routinely stained sections and four cases with morphologically uniform cell populations where the divergent differentiation was only detected immunohistochemically. The tumors occurred in adults (age range, 48-81; mean, 68); there were two men and three women. None of the patients presented with symptoms related to either enzyme or hormone liberation. Histologically, the tumors were very cellular; various combinations of solid, trabecular, acinar, and glandular growth patterns were noted. The cells contained d-PAS-positive granules and showed immunohistochemical positivity for pancreatic enzymes (trypsin, chymotrypsin, and lipase) and endocrine markers (chromogranin and synaptophysin); specific endocrine hormones were found in two cases. Double immunohistochemical staining for acinar and endocrine markers showed that most cells expressed only one line of differentiation. Ultrastructural study of two cases showed two populations of granules. Two of the patients died of their tumors (mean survival, 10.5 months), one with widespread metastases. Two patients were alive with disease at 12 months after diagnosis, and one patient was lost to follow-up after 3 months. This rare type of pancreatic neoplasm provides further evidence of the close histogenetic relationship between the exocrine and endocrine components of this organ.
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PMID:Mixed acinar-endocrine carcinomas of the pancreas. 803 90

Very little is known about factors influencing the migration of highly activated T-lymphocytes. One such lymphocyte population is the IL-2 expanded population of T cells infiltrating tumors. These tumor-infiltrating lymphocytes (TIL) can cause tumor regression in patients with metastatic cancer and in murine tumor models when given in adoptive transfer. In patients with melanoma, these TIL have been shown to migrate to sites of tumor and this may be a critical factor in their antitumor activity. In this study, a 48-well microchemotaxis chamber and a 5 microns pore nitrocellulose filter membrane system was utilized to study the motility of murine TIL. A chemotactic response was observed to supernatants from freshly explanted, autologous, and nonautologous tumor cultured for 24 h. Serially passaged autologous and nonautologous tumors also produced supernatants with chemotactic activity. Supernatants from single cell suspensions of normal tissues prepared and cultured identically did not elicit chemotaxis. Chemotactic activity for TIL was not removed by dialysis (2000 MW exclusion limit), its activity was undiminished by heat treatment at 60 degrees C for up to 60 min, and it was trypsin sensitive. Tumor supernatants were also chemotactic for two IL-2-dependent specifically alloreactive CTL lines (CTL-TIM and OE-4), but not two helper T cell lines (D-10 and D-1.5) or normal resting lymphocytes. This is the first demonstration of a chemotactic effect on IL-2-dependent, activated T cells. Characterization and purification of factors from tumor responsible for this directed migration are in progress.
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PMID:A tumor-elaborated supernatant factor chemotactic for IL-2 expanded tumor infiltrating T-lymphocytes. 845 27

Tumor-stromal interactions appear to play an important role in the induction of metalloproteinase expression in malignant tumors. We describe a tissue culture system in which expression of MMP-9 (gelatinase B or the 92 kDa type IV collagenase/gelatinase) was induced by co-cultivation of fibroblasts with breast cancer cell lines. While neither the breast cancer cells nor the normal rat embryo fibroblasts made MMP-9 alone in culture, human MMP-9 was made in the co-cultures. The MMP-9 was secreted in a latent form. The induction occurred at least in part through increases in the MMP-9 mRNA levels in the breast cancer cells. These increases did not appear to require protein synthesis. Conditioned medium from the fibroblasts could duplicate the induction of MMP-9 in the breast cancer cell lines. The active factor in the medium was inactivated by heat or by trypsin suggesting that it was a protein. This protein was in the size range of 30-100 kDa. Thus, fibroblasts could secrete a factor which was able to regulate the expression of MMP-9 in breast cancer cells.
Clin Exp Metastasis 1996 May
PMID:Induction of matrix metalloproteinase 9 expression in breast carcinoma cells by a soluble factor from fibroblasts. 867 73

It is widely recognized that matrix metalloproteinases and serine proteinases play an important role in cancer invasion and metastasis. We have reported that trypsin is synthesized in ovarian carcinomas as well as in some other types of cancers. In general, ovarian cancers easily tend to invade, metastasize, and spread widely into the peritoneal cavity. However, low-malignant-potential (LMP, borderline tumor) ovarian tumors are known to have limited malignant potential for progression, although microinvasion and distant metastasis have been reported among them. To analyze the relationship between varied degrees of trypsin expression and malignant behavior of ovarian tumors, immunohistochemical studies with monoclonal antibodies to human trypsin and clinicopathologic analysis were performed in human ovarian carcinomas, low-malignant-potential tumors, and benign cystadenomas. Thirteen (44.8%) cases of 29 ovarian carcinomas showed prominent trypsin expression, while only 2 (18.2%) cases of 11 LMP ovarian tumors demonstrated low levels of expression. Benign tumors and normal ovaries did not show any positivity for trypsin. These data suggest that tumor-derived heterotropic trypsin may be associated with ovarian tumors in parallel with malignant potential or behavior such as invasiveness or metastasis. At least in some ovarian carcinomas, prominent stromal invasion or metastasis might require the acquisition of or association with tumor-derived trypsin production.
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PMID:Differential expression of trypsin in human ovarian carcinomas and low-malignant-potential tumors. 951 1

Expression of KAI1, a tumor metastasis suppressor gene, was studied with different fixatives in frozen and paraffin-embedded sections of human and rat prostate carcinoma cell lines and human prostate lesions by immunohistochemistry. Immunoreactivity of the membrane antigen in cell lines was associated with known expression levels in these lines and the fixative used. Formalin and paraformaldehyde helped maintain the immunoreactivity of cells. In human prostate, frozen sections revealed diffuse reactivity of the antigen in normal and neoplastic tissues while paraffin-embedded tissues usually showed focal reactivity, although more than 50% of cases with normal epithelium and adenocarcinomas were reactive. In some cases, pretreatment with trypsin enhanced immunoreactivity. Benign prostatic hyperplasia (BPH) showed the most intense diffuse immunoreactivity, which suggested enhanced expression. Prostatic intraepithelial neoplasia (PIN) also often expressed high levels of KAI1. Three of five metastases were reactive but two primaries and their metastases were not. Lymphocytes in primary carcinomas and lymphocytes and germinal center cells in lymph nodes were immunoreactive, while adjacent primary or metastatic prostate adenocarcinoma epithelium was not immunoreactive. Although paraffin-embedded human tissues were not optimal for determining levels of expression of KAI1, they did show immunoreactivity that could have prognostic value and showed the specific cytoplasmic localization of the protein in cells.
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PMID:Expression of KAI1 in paraffin-embedded normal, hyperplastic and neoplastic prostate and prostate carcinoma cell lines. 958 71

Tumor growth beyond a certain size requires angiogenesis. Experimental evidence shows that once tumors leave the pre-angiogenic phenotype to become angiogenic, metastases often start to evolve. The aim of this study was to develop a reproducible immunohistochemical technique and method to characterize the neovascularization in archival prostate cancer tissue by quantifying the microvessel density (MVD). Archival tumor specimens from 64 consecutively diagnosed prostate cancer patients were immunostained for von Willebrand Factor (vWF), endothelial antigen and for CD31 combined with the use of different digestive enzymes (trypsin and pronase) and heating in a microwave oven. Both the mean and the maximal MVD, and the reproducibility of the method were estimated. Finally, the mean MVD, the maximal MVD, and clinical characteristics were correlated with the crude survival of the patient population. The immunohistochemical staining for vWF to measure the maximal MVD was found to be a reproducible method of characterizing the individual tumor. Both a univariate and a multivariate analysis demonstrated that the maximal MVD, in contrast to the mean MVD, was significantly associated with survival in prostate cancer patients. We conclude that evaluation of angiogenesis by immunostaining the endothelial cells for vWF measured by the MVD in the most vascularized areas of the tumor is a reproducible method of characterizing the individual prostate tumor. Maximal MVD proved to be an independent prognostic parameter useful in conjunction with other known prognostic markers in human prostate cancer.
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PMID:Immunohistochemical determination of tumor angiogenesis measured by the maximal microvessel density in human prostate cancer. 963 68

Metastasis is a characteristic and fatal feature of human malignancies. Its regulation is therefore of the utmost significance to clinicians. The present study was undertaken to determine whether a legume-derived protease inhibitor (PI) of trypsin/chymotrypsin, the field bean PI (FBPI), also has plasmin inhibitory activity and can inhibit pulmonary metastasis of B16F10 melanoma cells systemically injected into BDF1 mice. Two approaches to the problem were made. In the first, the melanoma cells were exposed to two different concentrations of the FBPI prior to their inoculation into animals. In the second, the mice were treated intraperitoneally with FBPI at a dose of 100 mg/kg body weight once daily for 10 days, the treatment being started soon after the systemic injection of the tumour cells. The study revealed that both modes of FBPI treatment could effectively block lung cell metastasis by the melanoma cells and that FBPI has plasmin blocking activity. Since urokinase type plasminogen activator and plasmin are known to play significant roles in tumour cell metastasis, the dose-dependent inhibitory effect of FBPI with antiplasmin activity on tumour cell metastasis suggests that its antimetastatogenic action is probably mediated through its plasmin inhibitory action.
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PMID:The field bean protease inhibitor has the potential to suppress B16F10 melanoma cell lung metastasis in mice. 971 30

Some proteolytic enzymes, trypsin, cathepsin B, cathepsin D, collagenase, elastase and their inhibitors, API and AMG, in serum of patients with colorectal carcinoma have been evaluated. Twenty patients belonged to stage B of colorectal carcinoma, twenty two patients to stage D (Astler and Coller classification) and a control group of thirty healthy volunteers were evaluated. Except in cathepsin D, patients exhibit higher enzymatic activities than healthy subjects, and both groups have all the proteolytic activities assayed in serum. Patients with disseminated disease have increased cathepsin B and collagenase levels, with a decrease of trypsin activity, showing an increment in API and AMG in sera. However, only the API values were significantly higher in patients with metastases. The coexistence of proteolytic activities in human sera together with their inhibitors is considered as well as the origin of these, tumoral and/or reactive, increments. Cathepsin B levels are raised in colorectal neoplasms and contribute to the destruction of the extracellular matrix and the proliferation of tumoral cells. There is evidence that a relation between collagenase like activity and tumor invasiveness exists. Cathepsin B and collagenase increases agree with the tumoral mass. On the other hand, trypsin decrease in metastatic carcinoma is probably related to the increment of their inhibitors, API and AMG, acute phase reactant proteins.
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PMID:Serum proteolytic activities and antiproteases in human colorectal carcinoma. 973 3

It has previously been reported that the trypsinogen gene is expressed in various human cancers. To investigate the possible role of trypsin in tumor malignancy, trypsinogen-1 cDNA was introduced into the human gastric carcinoma cell line MKN-1. The overexpression of trypsinogen-1 in MKN-1 cells stimulated cellular growth and adhesion to fibronectin and vitronectin when the trypsinogen activator enterokinase was added into the culture. Enterokinase treatment of the conditioned medium of the MKN-1 transfectants partially converted the proforms of gelatinases B and A to their apparent active forms. When the MKN-1 transfectants expressing trypsinogen-1 were intraperitoneally transplanted into nude mice, the mice frequently produced tumors in the colon, spleen and liver. However, the mice implanted with control MKN-1 cells produced no tumors. These results strongly suggest that tumor-derived trypsin contributes to the disseminated growth of some types of cancer cells including gastric cancer.
Clin Exp Metastasis 1998 Oct
PMID:Stimulation of cellular growth and adhesion to fibronectin and vitronectin in culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells. 993 8


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