Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The serial levels of fibronectin (FNp) in plasma from 65 patients with benign and malignant breast disease and from 74 healthy control women were assayed by the use of the rocket immunoelectrophoresis procedure. Mean FNp levels in patients with breast cancer were age-matched with control subjects, but no clear correlation was found between FNp levels and the presence of primary tumor. Mean FNp values for fibroadenoma patients did not differ either from controls or from patients with malignant disease. Patients were also categorized according to TNM classification, to the number of positive axillary nodes, to the histologic grade of malignancy, and to the presence of estrogen receptors. Although differences were not significant, a higher number of patients with levels greater than the normal 95% percentile were found only in the group with four or more positive axillary nodes and in the group with a greater number of histologic malignancies. Marked fluctuations in FNp concentrations were found in individual patients during the follow-up period, independently of the treatment received. FNp seems unsuitable as a tumor marker because, besides its apparent lack of specificity for cancer, it reflected neither the host-tumor burden nor the response to treatment.
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PMID:Serial analysis of fibronectin concentration in plasma of patients with benign and malignant breast diseases. 394 15

In this review some of the major mechanistic pathways by which tumor cells are thought to invade host tissues are discussed. Tumor invasion has been conceived to be the result of pathological, close-range interactions between malignant cells and host stroma. The sequence of events that characterize invasion can be summarized as follows: (a) Tumor cell clusters break from the confinement of the primary tumor. Loss of intercellular junctions (desmosomes), alterations in the chemical composition and physical properties of the cell surface coat (loss of fibronectin and heparan sulfate; excessive amounts of hyaluronate), and loosening of cell-substrate interactions (loss of hemidesmosomes, fibronectin, and heparan sulfate), are among the most frequently listed causes of tumor cell shedding. (b) Increased proteolytic activities at the invasion front cause focal alterations in the surrounding extracellular matrix, thereby changing its physical properties. Collagenases and cathepsins, as well as elastase and other neutral proteinases are the enzymes most frequently associated with matrix destruction and invasion. In some tissues this process is effectively regulated by inhibitors of matrix-degrading, proteolytic enzymes. (c) Tumor cells migrate into the altered matrix, possibly moving as aggregates along guidance tracks provided by host structures (blood vessels, lymphatics, nerves) or matrix macromolecules (collagen and fibronectin tracks). Migration seems to be preceded by increased swelling of glycosaminoglycan (i.e., hyaluronate) in the matrix, ahead of the migrating cell population. Various host cell types (mast cells, fibroblasts, endothelial cells, macrophages, etc.) may participate in these events.
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PMID:Tumor invasion and host extracellular matrix. 635 11

Randomly chosen clones of the murine K-1735 melanoma tumor were used by Raz and Geiger to address the question of whether variations in actin organization in these cells may be related to their lung colonization capability in syngeneic hosts (Cancer Res., 42: 5183-5190, 1982). In 14 of 15 clones tested, we found that the degree of actin organization was inversely correlated to their metastatic capability. We have further shown that remarkable variations exist in the adhesive properties and locomotor activity of four K-1735 melanoma cell variants that exhibit distinct metastatic properties. The low-metastatic cell variants displayed large focal adhesion plaques, tightly packed actin bundles, elaborate extracellular networks of fibronectin, and restricted motility. In contrast, the high-metastatic variants were poorly attached with only few distinct actin bundles, were unable to reorganize extracellular fibronectin into cables, and exhibited high motile activity. Electron microscopic examination of local s.c. tumors of the high- and low-metastatic lines indicated that the former formed loose tumor masses with very few intercellular connections, while the low-metastatic line developed into a considerably more compact tumor with numerous intercellular contacts, in line with the in vitro findings. It is proposed that the differences in cellular properties manifested by these cell lines may be related to their metastatic properties. Specifically, the highly metastatic cells of this tumor system may easily detach from the primary tumor mass, form weak and transient connections with surrounding connective tissue, and actively migrate through it. Furthermore, these results point to the close interrelationships between different mechanochemical features in cells, including specific cell adhesiveness, cytoskeletal organization, locomotion, and rearrangement of extracellular fibronectin. The possible nature of these interrelationships is discussed.
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PMID:Motility and adhesive properties of high- and low-metastatic murine neoplastic cells. 669 79

In order to better understand the cellular mechanism of glioma invasion, we investigated migratory responses and adhesiveness of human malignant glioma cells to fibronectin (FN) or vitronectin (VN). In addition, an expression of integrin subunits for FN and VN was analyzed by flow cytometry. All glioma cells tested migrated to both FN and VN to a various degree. Glioma cells which strongly migrated to FN or VN showed an intense expression of alpha 5 or alpha v, respectively, while there was no correlation between cell adhesiveness to FN or VN and intensity of the integrin expression. Studies using primary tumor cells from surgical specimen revealed that only an intensity of cell adhesiveness to FN was negatively correlated well with the degree of clinical invasion of gliomas. That is, the more glioma cells adhered to FN, the less the original tumor tissues showed tumor invasion.
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PMID:[Migration and adhesiveness of malignant glioma cells to fibronectin or vitronectin and their expression of integrin subunits]. 754 63

Dissemination of tumor cells includes several steps, such as: (a) detachment of tumor cells from the primary tumor, (b) traversement of the basement membrane, and (c) migration into the extracellular matrix. In these processes, at least two important categories of proteins are involved: proteases and adhesion molecules. In this contribution we describe the expression and function of components of the plasminogen activator (PA) system (proteases) and of integrins (cell-matrix adhesion molecules) in a panel of four human melanoma cell lines with different invasive and metastatic capacity. Regarding the components of the PA system, we found differences in expression of urokinase-type PA (uPA) and type 1 and 2 PA inhibitors (PAI-1 and -2) between metastasizing and nonmetastasizing cell lines. Both components were exclusively expressed in the highly invasive and metastatic cell lines. Interestingly, studies on the expression of PA components in fresh human melanocytic lesions, showed expression of these components exclusively in advanced primary melanomas and melanoma metastases. Regarding integrin expression we found elevated levels of VLA-2 and VLA-6 in the highly invasive and metastatic cell lines compared with normal cultured melanocytes and nonmetastatic melanoma cell lines. In addition, increased adhesion of the highly metastatic cell lines to laminin (LM) and collagen (COLL) was observed. Furthermore, reduced adhesion of normal melanocytes and nonmetastatic melanoma cells to LM and CO was mainly due to the fact that the integrins involved in adhesion to these matrix components were present in an inactive state. Finally, differences were observed in expression of integrins involved in adhesion to fibronectin.
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PMID:Properties of metastasizing and nonmetastasizing human melanoma cells. 759 84

The antitumor effects of biological response modifiers (BRM) in an experimental mouse model, the "double grafted tumor system," were analysed. Intratumoral administration of PSK (polysaccharide Kureha), a Coriolus preparation into primary tumor induced a cure of not only the primary solid tumor but also the metastatic, distant tumor. The effect of PSK on in vitro invasion by murine RL male-1 leukemia cells was studied using Biocoat Matrigel Invasion Chamber (Becton Dickinson Labware). We determined the ability of tumor cells to penetrate matrigel-coated filters in the presence or absence of PSK. PSK (100 micrograms/ml) reduced to half the number of invasive tumor cells for 3 hr incubation. PSK inhibited tumor cell invasion of matrigel-coated filters in a dose-dependent manner. Matrigel includes laminin, collagen, fibronectin and heparan sulfate proteoglycan. It is possible, therefore, that PSK may inhibit enzymes which digest the components of basement membranes, extra cellular matrices (ECM). This phenomenon suggests that PSK also inhibits metastatic activity of tumor cells in vivo.
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PMID:[Antitumor effect of intratumoral administration of a Coriolus preparation, PSK: inhibition of tumor invasion in vitro]. 794 50

Cryosections from surgical tissue blocks of primary laryngeal carcinoma were examined by immunohistochemistry for the distribution of several extracellular matrix (ECM) proteins and of tumor infiltrating cells (TIC). For the assessment of ECM proteins 8 monoclonal antibodies (Moabs) versus fibronectin, its neoplastic isoforms, tenascin, type IV collagen, laminin were used. TIC were evaluated by means of 9 Moabs versus various lymphocyte subsets, NK cells and macrophages. Marked differences were found in overall normal ECM proteins expression between tissues free from neoplastic invasion, those of closest tumor vicinity and of tumor mass. ECM proteins were found to be the most abundant in remote, apparently normal tissue compartments. They were less expressed in direct tumor proximity and almost absent from tumor mass. On the contrary, fibronectin isoforms were absent in tissue areas free from tumor but became demonstrable in tumor mass and its close vicinity. Tumor infiltrating cells were quite abundant in direct tumor vicinity. While comparing an intensity of expression of ECM proteins and accumulation of TIC in laryngeal carcinoma, reverse correlations were noticed. Strong expression of normal ECM proteins was accompanied by relatively scarce lymphocytic infiltrates in areas distant from primary tumor, while in the tissues abundant in TIC accumulation, such as in direct tumor vicinity, only weak ECM protein expression was seen. This was not the case when fibronectin neoplastic isoforms were studied. The latter could be shown in proximity or within tumor mass exclusively.
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PMID:Extracellular matrix proteins expression and incidence of tumor infiltrating cells in laryngeal carcinoma. 795 34

Three human neuroblastoma cell lines, with or without N-myc amplification, were evaluated for their integrin expression patterns as cultured cells, as well as their nude mouse-borne tumors obtained after subcutaneous (ectopic) or adrenal gland (orthotopic) injection. IMR-32 and LaN1 cells (with amplified N-myc) do not express any of the common integrin subunits that recognize fibronectin or collagens, as determined by immunoprecipitation of cell extracts with specific monoclonal antibodies; the same was true for all subcutaneous or adrenal tumors from IMR-32 or LaN1, indicating that they are not essential during primary tumor formation at either site. SK-N-SH cells (with diploid N-myc) express beta 1, alpha 2, and alpha 3 subunits of expected sizes (with alpha 2 uncleaved at 145 kDa) but do not express alpha 1, alpha 4, alpha 5, alpha V, or beta 3. This expression pattern was conserved in all first-round subcutaneous and adrenal tumor cell populations, as well as in second-round subcutaneous tumors derived from a first-round subcutaneous tumor (no tumors expressed beta 3). One significant difference was noted between subcutaneous and adrenal tumor populations: all first- and second-round subcutaneous tumors expressed high levels of alpha V subunit, while adrenal tumors did not express any alpha V. This result suggests some essential function for alpha V beta 1 during subcutaneous primary tumor formation. Integrin patterns were also evaluated by fluorescence-activated cell sorting. SK-N-SH and its derivative tumors expressed heterogeneous amounts of beta 1 and alpha 2 at the cell surface, while only subcutaneous tumor cells expressed alpha V. Parental SK-N-SH cells contained two subpopulations, half of which expresses alpha 3, while the other half does not; all subcutaneous tumor cells retained this two-subpopulation pattern, indicating that primary tumor formation does not lead to clonal dominance of alpha 3- or alpha 3+ cell types in larger primary tumors. While these results suggest a correlation between N-myc amplification and down-regulation of integrin expression in neuroblastoma, they demonstrate conservation of integrin expression during two rounds of primary tumor formation at ectopic or orthotopic sites in a mouse model system, induction and/or selection for alpha V beta 1 expression at the subcutaneous site, and clonal heterogeneity in alpha 3 beta 1 expression throughout primary tumor development.
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PMID:Integrin expression in human neuroblastoma cells with or without N-myc amplification and in ectopic/orthotopic nude mouse tumors. 802 May 86

It is now clear that adhesive interactions play a critical role in the process of metastatic tumor dissemination. Adhesion molecules act as both positive and negative modulators of the metastatic process. Molecules such as E-cadherin that promote homotypic tumor cell adhesion function to maintain intercellular contacts that confine cells to the primary tumor site and are negatively correlated with metastatic potential. Because tumor cells are rapidly eliminated from the circulation, those cells that can quickly arrest in the vasculature at a secondary site and pass through the vessel wall into the surrounding tissue will have a selective advantage toward establishing new metastatic colonies. The first step in this process is specific adhesion to venular endothelial cells in selected organs, a process mediated by tumor cell surface molecules such as Sialyl LewisX or the VLA-4 (alpha 4 beta 1) integrin that mediate binding to endothelial adhesion molecules such as the E-selectin or the vascular cell adhesion molecule, VCAM-1. Site-specific endothelial determinants such as the lung endothelial cell adhesion molecule, LuECAM, may additionally specify particular sites for preferential adhesion and subsequent site-specific metastasis of particular tumor types. After adherence to endothelial cells and subsequent endothelial retraction, metastatic tumor cells must adhere to elements of the subendothelial basement membrane such as laminin and types IV and V collagen, interactions frequently mediated by members of the beta 1 and beta 4 integrin families. Finally, metastatic tumor cell adhesion to connective tissue elements such as fibronectin, type I collagen and hyaluronan, mediated by molecules such as the beta 1 integrins and by the CD44 cell surface adhesion molecule, are required for movement of tumor cells into the subendothelial stroma and subsequent growth at these new sites. Thus, metastatic potential can be influenced both positively and negatively by a variety of cell surface adhesive molecules that act both independently and in concert to direct tumor cells to particular tissues, allowing them to arrest in those tissues, migrate across the vessel wall and grow at the secondary site. In the current review, I discuss the nature of the adhesion molecules that have been implicated in the metastatic process, emphasizing those molecules that have been shown to correlate with metastasis in clinical human tumors or that have been shown to influence metastatic potential in in vivo experimental assays.
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PMID:Adhesion molecules in tumor metastasis. 840 Jan 43

Tumor cell adhesion to and migration through the extracellular matrix (ECM) can influence their capacity to disseminate. Since prior studies with Lewis lung carcinoma (LLC) tumors had shown metastatic clones to have more protein kinase A (PKA) activity than nonmetastatic clones, the present study assessed if PKA regulates the interaction between tumor and the ECM, and how this may be associated with the metastatic capacity of the tumor cells. This was accomplished with the use of metastatic (LLC-LN7) and nonmetastatic (LLC-C8) variants that had been stably transfected to overexpress the PKA Calpha subunit or to have blocked PKA activity. Cells with increased PKA activity were less adherent to vitronectin, laminin, and collagen I, and could more readily migrate through these ECM components than could transfectants with reduced PKA activity. PKA did not regulate adhesion to or migration through fibronectin, and did not appear to be associated with changes in expression of surface integrins. In addition to modulating tumor adhesion and migration in vitro, PKA activation caused an increased formation of metastases from s.c. tumors, but did not regulate formation of experimental metastases by i.v. injected tumor cells. These results suggest that PKA signaling is important for modulating the tumor-ECM interaction and can facilitate tumor transit from the primary tumor site.
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PMID:Protein kinase A regulates Lewis lung carcinoma adherence to extracellular matrix components and spontaneous metastasis. 867 86


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