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)

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

We established an in vitro peritoneal dissemination model using six ovarian cancer cell lines and cultured mesothelial cells. Ovarian cancer cells were classified into two types, invasive or adhesive, on the basis of their interaction with the mesothelial cell monolayer. The ovarian cancer cell lines derived from mucinous cystadenocarcinoma, poorly differentiated adenocarcinoma and undifferentiated carcinoma, which belonged to the invasive type, began to invade beneath the mesothelial monolayer from several hours after seeding in vitro, expelling the mesothelial cells at the periphery and forming colonies directly on the dish surface. On the other hand, cancer cell lines of clear cell carcinoma, which belonged to the adhesive type, showed colony formation with adhesion on the mesothelial monolayer even 18 h after seeding. Invasive-type cell lines invaded into the mesothelial monolayer at various rates in vitro, and the degree of invasiveness showed good correlation with the degree of peritoneal dissemination in vivo after intraperitoneal injection of cancer cells into nude mice. Adhesive-type cells showed rather higher dissemination rates in vivo. Microscopic observation of in vivo peritoneal dissemination at one day after inoculation also revealed two patterns of peritoneal involvement similar to those in vitro. In the in vitro model, anti-integrin alpha 2- and beta 1-antibodies inhibited the infiltration of invasive-type cells into the mesothelial monolayer, but did not affect colony formation by adhesive-type cells on the monolayer, indicating that invasion by both cell types was mediated by different molecules. This in vitro model is thought to be useful for analysis of the molecular mechanisms of peritoneal dissemination.
Invasion Metastasis 1995
PMID:Two distinct patterns of peritoneal involvement shown by in vitro and in vivo ovarian cancer dissemination models. 754 53

Integrin plays an important role in tumor metastasis through its interaction with extracellular matrix and endothelial cell. We have examined the role of each integrin in tumor metastasis by using transfection of integrin cDNA into various cells. Transfection of integrin alpha 2 subunit into RD cells, human rhabdomyosarcoma cells which do not express integrin alpha 2 beta 1, potentiated the frequency of metastases in various organs; lung, bone, adrenal gland, lymph node. alpha 4-transfectant of Chinese hamster ovary (CHO) cells, which do not have alpha 4 beta 1 on the cell surface, metastasized to bone through its interaction with VCAM-1 in the bone marrow stroma cells. On the other hand, alpha 5-transfectant of CHO cells was much less tumorgenic than parent CHO cells. These data suggest integrin influence tumor metastasis sometimes favorably and sometimes unfavorably according to the activity and the balance of various integrins.
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PMID:[Analysis of the mechanism of tumor metastasis by the transfection of integrin cDNA]. 763 1

Integrins are the major family of cell surface receptors that mediate adhesion to the extracellular matrix and sometimes cell-cell adhesive interactions. These integrin-mediated adhesive interactions are involved in the regulation of many cellular functions, including embryonic development, tumor cell growth and metastasis, programmed cell death, hemostasis, inflammation, immune reaction, bone reabsorption, etc. Integrins are composed of alpha and beta transmembrane subunits selected from among 16 alpha and 8 beta subunits that heterodimerize to produce more than 20 different receptors which bind specific ligands. Integrins link to intracellular cytoskeletal complexes and bundles of actin filaments. There have been many reports about intracellular signaling pathways activated by integrin-ligand interactions. Integrin may play an important role in tumor metastasis through its interaction with extracellular matrix and endothelial cell. We have examined the role of each integrin in tumor metastasis by using transfection of integrin cDNA into various cells. Transfection of integrin alpha 2 subunit into RD cells, human rhabdomyosarcoma cells which do not express integrin alpha 2 beta 1, potentiated the frequency of metastases in various organs; lung, bone, adrenal gland, lymphnode. alpha 4-transfectant of Chinese hamster ovary (CHO) cells, which do not have alpha 4 beta 1 on the cell surface, metastasized to bone through its interaction with VCAM-1 in the bone marrow stroma cells. On the other hand, alpha 5-transfectant of CHO cells was much less tumorigenic than parent CHO cells. These data suggest integrin influence tumor metastasis sometimes favorably and sometimes unfavorably according to the activity and the balance of various integrins.
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PMID:[Adhesion molecules and cancer metastasis]. 930 10

We investigated the expression of VLA-2 in gastric cancers by immunohistochemistry using anti-integrin alpha 2 and beta 1 antibodies and the data were compared with the pathological findings of each gastric cancer. The specimens were stained with an immunohistological technique for integrin alpha 2 and beta 1 subunits. Tumors, simultaneously expressing both integrin alpha 2 and beta 1 subunits were defined as positive for VLA-2. Tumors expressing either subunits of integrin alpha 2 or beta 1 or those showing reduced expression of both subunits were defined as VLA-2 negative tumors. In the 77 primary tumors, 55 (71%) were VLA-2 positive. 38 (90%) of 42 tumors showing differentiated type including tubular adenocarcinoma and papillary adenocarcinoma expressed VLA-2, whereas 19 (55%) out of 35 undifferentiated type of cancers including poorly differentiated adenocarcinoma, mucinous carcinoma and signet ring cell carcinoma stained for VLA-2. In the undifferentiated type of cancers, VLA-2 negative tumors had a significantly higher incidence of vessel invasion than VLA-2 positive ones (p<0.05). VLA-2 negative tumors showed a tendency to peritoneal dissemination, lymph node metastases, lymphatic invasion or invasion beyond the subserosal layer. In the specimens of peritoneal dissemination, VLA-2 expression rate was found in 56% (9/16), with a higher expression rate than that of primary lesions. These data indicate that reduced expression of VLA-2 may strongly associate with vessel invasion especially in the undifferentiated type of adenocarcinoma of the stomach.
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PMID:Association of progression and reduced expression of VLA-2 in gastric cancer. 2159 Feb 34