Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monoclonal antibody (mAb) 376.96 has been used for detection of micrometastatic tumor cells due to its high binding specificity for a wide range of tumor cells, but the identity and function of its target antigen have not been known. Here, using immunoprecipitation and siRNA technology, we demonstrate that the antigen is the human 4Ig-B7H3 (4Ig-hB7H3) protein, previously known as an immunoregulatory protein in immune cells. Immunoblots of whole cell lysates, subcellular fractionation and tunicamycin treatment of human tumor cells indicated that 4Ig-hB7H3 is a approximately 100-kDa N-linked glycosylated membrane protein. The tumor promoter phorbol 12-myristate 13-acetate (PMA) enhanced the expression of 4Ig-hB7H3 in FEMX-I (melanoma), MA11 (breast cancer), and OHS (osteosarcoma) cells, suggesting that 4Ig-hB7H3 may be implicated in tumorigenesis. Most importantly, siRNA-downregulation of hB7H3 reduced cell adhesion to fibronectin of melanoma and breast cancer cells by up to 50 %, and migration and matrigel-invasion by more than 70 %, but surprisingly had no apparent impact on cell proliferation. In conclusion, our data present 4Ig-hB7H3 as a tumor-associated antigen and suggests a novel biological role of 4Ig-hB7H3 in tumor progression and metastasis.
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PMID:The immunoregulatory protein human B7H3 is a tumor-associated antigen that regulates tumor cell migration and invasion. 1869 Aug 46

We have recently demonstrated strong nuclear deformation of SaOs-2 osteosarcoma cells on poly-L-lactic acid (PLLA) micropillar substrates. In the present study, we first demonstrated that chemical and mechanical properties of the micropillar substrates have no dominant effect on deformation. However, SaOs-2 nucleus deformation could be strongly modulated by varying the pillar size and spacing, highlighting the importance of geometric constraints for shaping the nucleus. Furthermore, comparing the capacity for nuclear deformation in three different osteosarcoma cell lines (SaOs-2, MG-63 and OHS-4) revealed strong cell-type specific differences. Surprisingly, the highly-deformable SaOs-2 cell line displayed the highest cell stiffness as assessed by AFM-based colloidal force spectroscopy and featured a more prominent array of actin fibres above the nucleus, suggesting a link between actin-mediated cell stiffness and cell nucleus deformation. In contrast, in MG-63 and OHS-4 cells dense microtubule and vimentin networks seem to facilitate some nuclear deformation even in the absence of a prominent actin cytoskeleton. Together these results suggest that an interaction of all three cytoskeletal elements is needed for efficient nuclear deformation. In conclusion, the dominant parameters influencing nuclear deformation on micropillar substrates are not their material properties but the substrate geometry together with cell phenotype and cytoskeleton organization.
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PMID:Directing nuclear deformation on micropillared surfaces by substrate geometry and cytoskeleton organization. 2335 73

A promising method that offers both time- and site-specific delivery of macromolecules is photochemical internalization technology (PCI). Here, we have characterized various polyamidoamine (PAMAM) carriers [generation (G) 0-7], for light-directed delivery of nucleic acids in vitro by the use of PCI technology. A number of parameters for optimal delivery of nucleic acids into human cancer cells, that is, various light-doses, carrier-doses, and small interfering RNA (siRNA)/messenger RNA (mRNA) doses were investigated for either up- or down-regulation of enhanced green fluorescent protein (EGFP) gene expression. In summary, our results showed in an osteosarcoma cell line (OHS) [EGFP] model system the possibility for efficient light-directed siRNA silencing (>80% silencing) when using PAMAM G3 to G7 as carriers. Surprisingly, no EGFP mRNA up-regulation was detected either with or without PCI after EGFP mRNA/PAMAM (G0-G7) transfection in standard OHS cells. We have here identified properties for PAMAM formulations enabling light-directed siRNA delivery with the aim of developing a site-specific strategy for delivery of nucleic acids in vivo.
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PMID:Light-controlled modulation of gene expression using polyamidoamine formulations. 2353 Jun 84


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