Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined 92 patients with epithelial ovarian cancer and 262 patients with benign ovarian diseases undergoing laparotomy. On the basis of a nonparametric method, antigen levels corresponding to prefixed 95% specificity values in a group of 674 women with benign gynecologic diseases were taken as cutoff limits (88.8 U/ml for CA 125 and 13.7 U/ml for CAM 29). Moreover, CA 125 and CAM 29 levels were measured serially during and after chemotherapy in 26 women selected from the patients with advanced epithelial ovarian cancer. At diagnosis, serum CA 125 was as sensitive as serum CAM 29 for nonmucinous tumors, but more sensitive than serum CAM 29 for mucinous tumors. The association of the two markers seemed to give no advantage over the CA 125 assay alone in the diagnosis of epithelial ovarian cancer. In monitoring the response to chemotherapy and follow-up of patients with epithelial ovarian cancer, changes in CA 125 levels correlated with the clinical course of disease better than changes in CAM 29 levels, and the serum CA 125 assay was more reliable than the serum CAM 29 assay in the early detection of tumor progression. In conclusion, serum CAM 29 did not seem to represent a complementary assay to serum CA 125 in the management of patients with epithelial ovarian cancer.
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PMID:Combined evaluation of serum CA 125 and CAM 29 in patients with epithelial ovarian cancer. 129 26

The transformation of a potentially neoplastic cell into an autonomous highly malignant and metastatic tumor cell involves a multifactorial cascade of events. This will eventually lead not only to the emergence of a tumor cell with an unlimited potential of replication, but more important will contribute to its ability to ignore and evade homeostatic immune and non-immune regulatory mechanisms. Specifically, those mechanisms which may restrict and direct its growth, dissemination, patterns of differentiation and interaction with the cellular and humoral factors comprising its environment. However, many different factors may contribute to a highly invasive and malignant phenotype. It is obvious that one should expect that a cardinal role should be assigned to alterations in those factors which contribute to the capacity of the malignant cells with its environment at the cell membrane level, which in turn is dependent on the concerted functional expression of specialized membrane associated components (i.e. receptors, cyto adhesion molecules (CAM's), histocompatibility antigens, GAP junction complexes, extracellular matrix components, etc.). In the present studies, we have investigated the contribution of three major factors, which maybe the cause or result of alterations at the level of the cell membrane: MHC encoded antigen expression, susceptibility to the cytolytic activity of NK cells and enhanced expression of the c-K-ras proto-oncogene, as to their development of metastatic capacity of a malignant cell. To address these questions, we used metastatic (IE7) and non-metastatic (IC9) variants of the murine 3-methylcholanthrene induced T-10 fibrosarcoma. Using this system, the following major conceptually important observations were made: A. The restoration by transfection of the expression of membrane associated H-2K encoded glycoproteins abrogates the metastatic capacity of the highly metastatic tumor cell clone, IE7, irrespective of the degree of susceptibility to NK or c-K-ras oncogene expression. This reduction in metastatic capacity is followed by a significant decrease in its tumorigenicity which is concomitant with its ability to induce in vivo potent H-2K restricted CTL's. These results clearly indicate that H-2K region encoded molecules play no apparent role in determining the susceptibility of tumor cells to NK cells, and yet their loss or aberrant expression is a cardinal event in tumor progression towards metastatic capacity, a fact which is supported by similar observations achieved in other murine models (18).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:NK sensitivity, H-2, c-K-ras proto-oncogene expression and metastases: analysis of the metastatic potential of H-2 gene transfected fibrosarcoma cells. 306 49

Cell adhesion molecules have been suggested to function as tumor suppressor molecules. We have been studying one of the epithelial cell adhesion molecules (C-CAM), which belongs to the immunoglobulin gene superfamily. Transfection of a C-CAM cDNA expression vector into a highly tumorigenic human prostate cancer cell line (PC-3) suppresses tumor formation in nude mice. Alternatively, reducing C-CAM expression levels in the nontumorigenic rat prostate epithelial cell line NbE by the antisense expression vector markedly increases tumorigenicity of NbE cells in nude mice. These results suggest that C-CAM may be a tumor suppressor in prostate cancer. In this study, we examined the relationship between C-CAM expression during human prostate development and neoplastic progression by immunohistochemical staining of frozen sections. C-CAM predominantly localized on the plasma membrane of the basal cell layer in both the fetal and normal adult prostate gland. However, an overall decreased staining was seen in benign prostatic hyperplasia and high grade prostatic intraepithelial neoplasia. Furthermore, C-CAM was not detected in prostate carcinomas. Thus, a decrease in C-CAM expression may be an early event in hyperplastic/neoplastic transformation. These observations support the suggestion that C-CAM is a tumor suppressor in prostate cancer progression.
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PMID:Consistent expression of an epithelial cell adhesion molecule (C-CAM) during human prostate development and loss of expression in prostate cancer: implication as a tumor suppressor. 753 59

Melanoma often develops from clinically and histologically well-defined precursor lesions. During progression of normal melanocytes to benign nevi, dramatic changes in the expression of adhesion receptors are observed, most notably loss of E-cadherin which mediates adhesion of melanocytes to keratinocytes, and gain of Mel-CAM which predominantly mediates heterotypic adhesion between cells. Major changes in adhesion receptors also occur when cells progress from dysplastic nevi or biologically early radial-growth-phase primary melanomas to biologically late (tumorigenic) vertical-growth-phase primary melanomas. The integrin subunit beta 3 is up-regulated, whereas other integrins such as alpha 6 beta 1 and alpha V beta 1 are down-regulated. This review highlights the major changes in adhesion receptor expression on melanocytes at various stages of tumor progression.
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PMID:Adhesion receptors in human melanoma progression. 765 8

This paper reviews the current advances in molecular genetics and biology of prostate cancer development. Many genetic alterations in prostate cancer have been identified. Some of these changes are early events and occur in prostatic intraepithelial neoplasia and primary cancer of prostate, some others occur in late stages of prostate cancer development. The significant genetic changes for prostate cancer include losses for chromosomes 8p, 5q, 13q, and so forth; gains for chromosomes 8q, 11p, 3q, and so forth; aneusomies of chromosomes 7 and 8; and allelic losses at chromosome regions 8p 12-21, 10q23-24, 16q22.1-24, and 7q31.1-31.2. The alteration of the p53 tumor-suppressor gene plays a role in a subset of advanced prostate cancer. Expressions of TGF-beta receptors, E-cadherin, C-CAM, KAI1, and some integrins have an inverse correlation with either prostatic carcinogenesis or progression of prostate cancer, or both. Protein expression of BCL-2 in prostate cancer is highly correlated with cancer progression and androgen-independent phenotype. More studies need to be performed to identify specific genes for those genetic alterations and to explore the clinical use of the known molecules in prostate cancer.
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PMID:Molecular advances in prostate cancer. 909 May 1

Mel-CAM (MUC18 or CD146) is a cell adhesion molecule sharing sequence homology with members of the immunoglobulin gene superfamily. Mel-CAM was originally described as a marker associated with invasion and metastasis in melanoma. We determined here the distribution and biological significance of Mel-CAM in normal, benign proliferative, and neoplastic breast ductal epithelium. Using a Mel-CAM-specific monoclonal antibody, we, immunohistochemically demonstrate Mel-CAM expression in 14 of 14 (100%) normal breast epithelia and benign proliferative ductal epithelial lesions, whereas Mel-CAM expression can only be focally detected in 12 of 72 (17%) breast carcinomas. Solid-phase cell adhesion assay revealed that breast carcinoma cells in culture express the ligand for Mel-CAM. Transfection of Mel-CAM cDNA into breast carcinoma cells induces a more cohesive cell growth pattern and establishes smaller tumors in immunocompromised mice than mock transfectants. In conclusion, Mel-CAM is distributed throughout normal and benign proliferative mammary ductal epithelium, but it is frequently lost in carcinomas; it functions as a heterophilic cell-cell adhesion molecule in breast epithelium, and loss of Mel-CAM expression in breast carcinoma may be an important step for tumor progression.
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PMID:The cell-cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma. 928 23

An immortalized implantation site intermediate trophoblastic cell line, IST-1, was established from a human placenta of 7 weeks gestation. IST-1 cells phenotypically resembled the implantation site intermediate trophoblastic cells in situ and expressed Mel-CAM (MUC 18 or CD146). Mel-CAM is a cell adhesion molecule belonging to the immunoglobulin gene superfamily. It is involved in heterophilic cell-cell adhesion and plays a role in several biological processes including tumor progression. We have previously shown that Mel-CAM was highly expressed in the intermediate (extravillous) trophoblast in the human implantation site. In this study we determined the function of Mel-CAM in the interaction of trophoblast and uterine smooth muscle in the implantation site. IST-1 cells failed to adhere to immobilized recombinant Mel-CAM in solid phase whereas the uterine smooth muscle cells did. The presence of the putative Mel-CAM ligand in smooth muscle cells was further supported by the finding that Mel-CAM-transfected but not the mock-transfected U937 leukemia cells bind to the confluent monolayer of uterine smooth muscle cells. IST-1 cells attached efficiently to the monolayer of the uterine smooth muscle cells and acquired a spindle-shaped morphology simulating smooth muscle cells. The cell binding was only marginally affected by Mel-CAM blocking antibodies. However, Mel-CAM blocking antibodies and recombinant Mel-CAM promoted cell migration from IST-1 cell spheroids on the smooth muscle monolayer. Taken together, our results suggest that IST-1 cells express Mel-CAM but not the putative Mel-CAM ligand. In contrast, the uterine smooth muscle cells express the putative Mel-CAM ligand which binds to Mel-CAM on the surface of the IST-1 cells. The interaction between Mel-CAM and its putative ligand confers a stationary phenotype for trophoblastic cells. These observations are consistent with an important role for Mel-CAM in limiting trophoblastic migration within the myometrium in the implantation site.
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PMID:Expression of Mel-CAM in implantation site intermediate trophoblastic cell line, IST-1, limits its migration on uterine smooth muscle cells. 970 64

The growth of solid tumors has been shown to depend on neovascularization. By understanding the mechanisms that control the neovascular response, it may be possible to design therapeutic strategies to selectively prevent or halt pathologic vascular growth and restrain cancer progression. Thrombospondin-1 is an extracellular matrix protein that among several functions suppresses capillary growth in angiogenesis assays. We have demonstrated that within the context of the mammary gland TSP1 can modulate normal development of blood vessels. Expression of TSP1 in transgenic animals under the control of the MMTV promoter was associated with a 50-72% reduction in capillary growth. In addition, TSP1 reduced tumor size in transgenic overexpressors. The data suggest an important role for TSP1 in modulating vascular growth in both normal and pathologic tissues. The antiangiogenic region of TSP1 has been mapped to the type I (properdin) repeats. To identify novel proteins with such a domain, we have cloned two cDNAs (METH-1 and METH-2) which also have antiangiogenic properties. In addition to carboxyterminal thrombospondin-like domains they also contain metalloproteinase and disintegrin sequences. Expression of both proteins is broad but nonoverlapping. Recombinant fragments from these sequences have strong antiangiogenic potential in the CAM and cornea pocket assays. At the same molar ratio, METH-1 and METH-2 are about 20-fold more potent than TSP1. We predict that these proteins are likely endogenous modulators of vascular growth with relevant therapeutic potential in cancer and other disease states.
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PMID:Antiangiogenic domains shared by thrombospondins and metallospondins, a new family of angiogenic inhibitors. 1066 3

Basal-cell adhesion molecule (B-CAM) is a 90 kDa cell surface glycoprotein of the immunoglobulin superfamily that functions as a laminin-binding receptor. B-CAM is upregulated following malignant transformation of some cell types in vivo and in vitro, thus being a candidate molecule involved in tumor progression. As cutaneous distribution and function of B-CAM are largely unknown, we have studied its expression and regulation in normal and diseased human skin. In normal skin, B-CAM was expressed by endothelial cells of dermal blood vessels. In contrast, B-CAM was strongly upregulated within the tumor tissue of both malignant and benign epithelial skin tumors, including basal cell carcinomas, squamous cell carcinomas, keratoacanthomas, and common warts. Transformation-associated upregulation was confirmed in vitro, but normal keratinocytes also expressed B-CAM under culture conditions. Interestingly, the basal epidermal layer of normal-appearing skin surrounding the tumors also expressed B-CAM, and B-CAM were induced on the basal and apicolateral surfaces of basal keratinocytes in inflammatory skin disorders suggesting transformation-independent mechanisms of epidermal induction of the B-CAM. Immunoelectron microscopy studies of cultured transformed keratinocytes revealed that B-CAM was expressed at cell-cell and cell-substrate contact sites. Halting proliferation of transformed keratinocytes through cytostatic drugs resulted in decreased B-CAM synthesis. Likewise, inducing terminal differentiation in keratinocyte cultures by increasing the Ca(2+) concentration in the medium decreased B-CAM expression. In contrast, both ultraviolet A and B irradiation of cultured human keratinocytes resulted in significantly increased expression of the B-CAM. Overall, it appears that B-CAM expression in human skin is associated with activated states of keratinocytes, and that B-CAM may be involved in cell-cell adhesion or migration, in addition to its known function as a laminin receptor. J Invest Dermatol 115:1047-1053 2000
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PMID:Basal-cell adhesion molecule (B-CAM) is induced in epithelial skin tumors and inflammatory epidermis, and is expressed at cell-cell and cell-substrate contact sites. 1167 46

Normal human melanocytes are interspersed singly among keratinocytes along the basement membrane of the epidermis, whereas melanoma cells readily adhere to each other during invasion of the dermis or distant organs. The tumorigenic and metastatic phenotype of melanoma cells often correlates with increased expression of cell-cell and cell-matrix adhesion receptors. Mel-CAM (MCAM, MUC 18, CD146) is a cell-cell adhesion receptor highly expressed by melanoma cells but not normal melanocytes. We show here that inhibition of Mel-CAM expression in metastatic melanoma cells using genetic suppressor elements of Mel-CAM cDNA leads to inhibition of adhesion between melanoma cells and to downregulation of the tumorigenic phenotype. Growth was not inhibited in genetic suppressor elements-transduced melanoma cells cultured in monolayers but was inhibited when cells were maintained anchorage-independently in soft agar and greatly reduced in immunodeficient mice. A three-dimensional epidermal skin equivalent model demonstrated that Mel-CAM allows melanoma cells to separate from the epidermis and invade the basement membrane zone and dermis. However, melanoma cells with little or no Mel-CAM were poorly invasive, possibly due to their loss of gap junctional communication. These results suggest the multifunctional role of a melanoma-associated cell-cell adhesion receptor in tumor progression.
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PMID:Mel-CAM-specific genetic suppressor elements inhibit melanoma growth and invasion through loss of gap junctional communication. 1149 90


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