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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of cellular adhesion in regional lymph node metastasis of solid tumors has been investigated. The data reviewed is based on studies in four different tumor models of human, rat and murine origin. An in vitro assay measuring tumor cell attachment to cryostat sections of normal peripheral lymph nodes, obtained from the species of tumor origin was used to compare the adhesion of tumor sublines with different metastatic potentials. A good correlation was found between tumor cell potential to metastasize to regional nodes and the adhesion to the sections in all models studied. The adhesion of all tumor lines could be blocked by Arg-Gly-Asp containing peptides while pretreatment of the cells with antibodies to integrins implicated beta 1 and beta 3 receptor complexes in the adhesion. Ligand binding assays provided indirect evidence that the preferential attachment of the metastatic tumor lines to the frozen sections was mediated via extracellular matrix proteins such as fibronectin, vitronectin and type IV collagen. As these basement membrane proteins have been localized to the outer surfaces of reticular fibers which are known to permeate the lymph node and trasverse the subcapsular sinus it is postulated that tumor cell attachment to these fibers may facilitate and possibly be required for tumor cell retention and growth in the invaded regional nodes.
Cancer Metastasis Rev 1991 May
PMID:Adhesion mechanisms in lymphatic metastasis. 191 72

Collagen breakdown, and thus bone resorption, can now be assessed by measuring the urinary excretion of the collagen crosslinks, pyridinoline (Pyd) and deoxypyridinoline (Dpd). In a pilot study we measured Pyd and Dpd in 20 patients with breast cancer, ten with known bone metastases and ten with no recognised metastases in bone or elsewhere after 1 year's subsequent follow up. Eight out of the ten patients with metastases had crosslink excretion values higher than the reference interval, but so did some patients without known metastatic disease. For both crosslinks there was a clear correlation with serum alkaline phosphatase activity measured at about the same time. We consider that measurement of urinary collagen crosslink assays may have a place in the early detection of metastatic spread to bone.
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PMID:Pyridinium crosslinks as markers of bone resorption in patients with breast cancer. 193 10

Laminin is a large glycoprotein that is found in basement membranes and promotes cell adhesion and migration. In human fibrosarcoma cells we detected the presence of an integrin complex, with a Mr of 140,000/120,000 under nonreducing conditions, that bound specifically to laminin-Sepharose columns. Immunoprecipitation with monoclonal antibodies characterized this complex as alpha 6 beta 1. Attachment of the fibrosarcoma cells to laminin substrates was completely inhibited in the presence of anti-alpha 6 beta 1 antibody, while attachment to fibronectin and type IV collagen was unaffected. When seeded onto reconstituted basement membrane, the fibrosarcoma cells spread out, migrated, and invaded the matrix. In the presence of anti-beta 1 or anti-alpha 6 beta 1 antibodies, initial invasion through the matrix was inhibited. The results indicate that the HT1080 cells express the alpha 6 beta 1 complex and that it mediates their attachment to laminin. Furthermore, this receptor appears to be important during initial attachment and subsequent invasion of basement membrane-like matrices.
Invasion Metastasis 1991
PMID:Role of laminin-binding integrin in the invasion of basement membrane matrices by fibrosarcoma cells. 193 74

The ability of cultured human fibroblasts to reorganize and contract three dimensional collagen I gels is regarded as an in vitro model for the reorganization of connective tissue during wound healing. We investigated whether adhesion receptors of the integrin family are involved. It was found that synthesis and transcription of the alpha 2 beta 1 integrin (but not of alpha 1 beta 1 or alpha 3 beta 1) is selectively upregulated when fibroblasts are seeded into type I collagen gels. Time course experiments revealed that high synthetic levels of alpha 2 beta 1 parallel the gel contraction process and return to "baseline" levels after the contraction has subsided. Furthermore, function-blocking mAbs directed to the alpha 2 and beta 1 chain of integrins inhibited gel contraction. Remodelling of connective tissue can be important for tumor cells during invasion and formation of metastases. Therefore, we tested human melanoma cell lines for this function. Five out of nine melanoma lines contracted collagen gels in vitro. Among these, two highly aggressive melanoma cell lines (MV3 and BLM) most efficiently contracted gels almost reaching the rate of normal adult fibroblasts. In these cells, synthesis of alpha 2 beta 1 was also significantly upregulated when seeded into collagen I gels. Moreover, function blocking anti-alpha 2 in conjunction with anti-beta 1 chain mAbs completely inhibited gel contraction for several days. Other melanoma cells (530) with lower metastatic potential which were not able to contract gels, showed no induction of alpha 2 beta 1 synthesis in gel culture. Our results suggest an important role of integrin alpha 2 beta 1 in the contraction of collagen I by normal diploid fibroblasts during wound healing and in the reorganization of collagen matrices by highly aggressive human melanoma cells.
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PMID:Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils. 195 83

Bone metastases in breast cancer may be osteolytic, osteosclerotic, or a mixture of the two. Although stimulation of bone resorption by breast cancer cells has attracted some interest, the formation of osteosclerotic secondary tumours and the influence of human mammary carcinoma cells on osteoblasts (bone forming cells), both important in understanding breast cancer--bone interactions, have been largely neglected. We therefore examined the effects of conditioned medium (CM) from two cultured human breast cancer cell lines (MCF7 and ZR-75) and from primary cultures of breast carcinomas from two patients, on osteoblasts and recruitment of bone-resorbing cells (osteoclasts) in vitro. Osteoblast-like cells (BDC) were cultured from human trabecular bone explants. Osteoclast maturation was studied in fetal rat calvaria cultured on collagen gels. CM from the MCF-7 line and cells derived from one patient each inhibited BDC DNA synthesis, but stimulated osteoclast recruitment. In contrast, CM from the second patient's cells or ZR-75 enhanced DNA synthesis in BDC, but blocked osteoclast maturation. This suggests that human breast carcinomas secrete soluble factors which influence both osteoclasts and osteoblasts. A further unexpected implication is that mammary carcinoma cells may cause local osteosclerosis by directly stimulating osteoblasts, rather than through raised bone turnover in metastases.
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PMID:Breast carcinomas synthesize factors which influence osteoblast-like cells independently of osteoclasts in vitro. 200 8

We have examined integrin expression and function in the human colon carcinoma cell line HT29, and in clonal sublines derived from the HT29 line. These cells express several different integrin subunits including beta 1, alpha 2, 3, 6 and alpha v, but do not express the classic alpha 5/beta 1 fibronectin receptor. Clonal variation in the pattern of integrin expression was quite limited. The profile of integrin expression correlates well with the adhesive behavior of HT29 cells. Thus the cells adhere well to vitronectin, laminin and type IV collagen, but not at all to fibronectin. Adhesion to collagen was completely blocked by an anti-beta 1 monoclonal antibody, indicating that beta 1 integrins mediate this process. Adhesion to laminin was strongly blocked by anti-beta 1 monoclonal or anti-beta 6 monoclonal, suggesting that the alpha 6/beta 1 complex functions in attachment to laminin; this was somewhat surprising since immunoprecipitation experiments indicate that most of the alpha 6 subunit seems to be associated with the beta 4 subunit. Despite their strong adherence to laminin, collagen and vitronectin, HT29 cells are not very motile and, in response to gradients of these proteins, do not migrate nearly as well as CHO cells tested under similar conditions. Since HT29 cells can undergo an enterocyte-like differentiation in glucose-free medium, we compared integrin expression in HT29 and its subclones during the process of differentiation. There was no correlation between the state of differentiation, as assessed by expression of brush-border hydrolases, and the level of expression of any of the integrin subunits measured. Thus the pattern of integrin expression in these colonic tumor cells seems to be a characteristic of the cell line, and is not readily modified by changes in cell growth or differentiation.
Clin Exp Metastasis
PMID:Expression and role of integrins in adhesion of human colonic carcinoma cells to extracellular matrix components. 203 21

We have previously reported that activated ras oncogenes can simultaneously switch on the metastatic phenotype and increased capability to degrade type IV collagen. Here the relationship between c-H-ras, metalloproteinase expression and metastatic behavior was studied in N-nitrosomethylurea (NMU)-induced rat mammary carcinomas, which are known to possess activated c-H-ras. When comparing normal rat breast tissue to mammary carcinomas there was no direct relationship between ras DNA levels and neoplastic changes. Furthermore, there were no consistent differences between metastatic and non-metastatic carcinomas, or between primary tumors and metastases. The NMU-induced rat mammary carcinomas expressed two major gelatinolytic metalloproteinases (gelatinases) of 65 and 92 kD, but only the 65 kD gelatinase was detected in normal breast tissue and a rat fibroma. Type IV collagenolytic activity per 5 micrograms of protein was two to three times higher in the mammary carcinomas than in the normal breasts, whereas the primary tumors did not differ from the corresponding metastases. This study shows that ras amplification is not necessary for development of the malignant or metastatic phenotype in the NMU-induced rat mammary carcinoma model. We have also found that induction of p21 ras protein synthesis in a v-H-ras transfected NIH/3T3 (433) cell line, containing a glucocorticoid promoter, does not lead to an increase in metastatic capacity.
Clin Exp Metastasis
PMID:Ras levels and metalloproteinase activity in normal versus neoplastic rat mammary tissues. 203 22

To investigate morphological features valuable in estimating the propensity of gastric cancer to metastasize to the liver, we examined the primary tumours from 49 surgically resected advanced gastric cancers (24 with liver metastasis) and 45 autopsy cases, 19 with liver metastasis. We paid special attention to extracellular matrices--connective tissue stroma and basement membrane (BM)--using immunohistochemistry and electron microscopy. Type IV collagen staining showed that in differentiated carcinomas neoplastic glands were occasionally located in close proximity to the BM of thin-walled tumour blood vessels in back-to-back fashion. In poorly differentiated lesions, tumour cells were also oriented toward the vascular BM in pseudorosette-like pattern. Type III collagen staining and electron microscopy showed that in such regions tumour cells, with continuous or discontinuous BM, were immediately adjacent to vascular BM with no connective tissue stroma in between. On occasion tumour cells were in direct contact with vascular BM. These close associations were often found in carcinomas with a medullary growth pattern, irrespective of the degree of histological differentiation. However, they were virtually never seen in their benign counterpart. Of the resected cases, all 24 with liver metastasis showed this association, whereas only 10 of 25 (40%) without liver metastasis did so (P less than 0.001). In the autopsied cases, a similar positive correlation was observed between liver metastasis and this association. Furthermore, the tumor cells showing this juxtaposition showed evidence of vascular invasion. These results suggest that the close association between tumour cells and vascular BM is specific to the malignant neoplasm, and may be related to liver metastasis. Immunohistochemistry can be a great help in estimating the probability of liver metastasis.
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PMID:Close association between tumour cells and vascular basement membrane in gastric cancers with liver metastasis. An immunohistochemical and electron microscopic study with special attention to extracellular matrices. 205 87

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

The lens of the eye is one of the rare organs in which tumors do not occur spontaneously. It therefore appeared to us that lens cells would not present the background of spontaneous transformation toward malignancy found with many other cell cultures. We have cultured C3H/HeA mouse lens explant (MLE) cells for 70 wk and analyzed changes in malignancy-related phenotypes in function of the number of passages. In vitro, we studied morphology, colony forming efficiency on tissue culture plastic substrate (CFEtc) and in soft agar, population doubling time, saturation density, and invasiveness into precultured chick heart fragments. In vivo, tumorigenicity, invasion, and metastasis were analyzed after injection of cell suspensions subcutaneously and intraperitoneally, after implantation of cells aggregated to collagen sponges under the renal capsule and after implantation of cell aggregates subcutaneously into the tail and into the pinna. The CFEtc, population doubling time, and saturation density increased as the number of passages of culture in vitro increased, but colony formation in soft agar was never observed. MLE cells till passage 16 were not invasive in vitro, but hereafter consistently were found to be invasive. After about 17 passages, corresponding to 25 wk of culture, MLE cells acquired the capacity to form tumors in syngeneic mice. These tumors were invasive but metastases were not observed. We concluded that MLE cells acquired in an apparently spontaneous way a number of malignancy-related phenotypes, without, however, reaching the stage of metastasis.
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PMID:Spontaneous acquisition of tumorigenicity and invasiveness by mouse lens explant cells during culture in vitro. 207 40


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