Tumors systemically initiate metastatic niches in distant target metastatic organs. These niches, composed of bone marrow-derived hematopoietic cells, provide permissive conditions for future metastases. However, the mechanisms by which these cells mediate outgrowth of metastatic tumor cells are not completely known. Using mouse models of spontaneous breast cancer, we show enhanced recruitment ...

Smooth muscle cells (SMCs) retain remarkable plasticity to undergo phenotypic modulation in which the expression of smooth muscle markers is markedly attenuated while conversely expression of extracellular matrix (ECM) is dramatically up-regulated. Myocardin is perhaps the most potent transcription factor for stimulating expression of smooth muscle-specific genes; little is known, however, abou...

Hyaluronan (HA) is a major component of the extracellular matrix (ECM) and is synthesized by three HA synthases (HAS). Similarities between the HAS2 knockout mouse and the hdf mutant mouse, which has a mutation in the versican gene, suggest that HA and versican expression may be linked. In this study, the relationship between HA synthesis and levels of versican, fibronectin and several other EC...

Objective: Expansion of the extracellular matrix is a prominent but poorly characterized feature of tendinosis pathology. We aimed to characterize the extent and distribution of the large aggregating proteoglycan versican in patients with patellar tendinosis. Methods: Tendon was obtained from tendinopathy patients undergoing debridement of the patellar tendon and from controls undergoing intram...

The versican (PG-M) gene encodes a chondroitin sulfate proteoglycan that is nonpermissive for cell migration and appears in association with slow cell proliferation and cytodifferentiation. Using the techniques of in situ hybridization and immunocytochemistry on sectioned mouse embryos, we found that the mRNA and protein for versican show similar distributions and are expressed in a dynamic pat...

To examine the biochemical influences that may contribute to the success of gene therapy for ocular disorders, the role of versican, a vitreous component, in adenoviral-mediated transgene expression was examined. Versican is a large chondroitin sulfate-containing, hyaluronic acid-binding proteoglycan present in the extracellular matrix and in ocular vitreous body. Y79 retinoblastoma cells and C...

Malignantly transformed cells usually display a rosette-like morphology of substratum adhesions (called podosomes) and disorganized microfilaments, and are often associated with elevated production of chondroitin sulphate. We previously showed that many tissues and cells express alternatively spliced multiforms of the large chondroitin sulphate proteoglycan termed PG-M (versican is one of the s...

The core proteins of large chondroitin sulfate proteoglycans contain a C-type lectin domain. The lectin domain of one of these proteoglycans, versican, was expressed as a recombinant 15-kDa protein and shown to bind to insolubilized fucose and GlcNAc. The lectin domain showed strong binding in a gel blotting assay to a glycoprotein doublet in rat brain extracts. The binding was calcium dependen...

Versican is a hyaluronan-binding, large extracellular matrix chondroitin sulfate proteoglycan whose expression is increased in malignant melanoma. Binding to hyaluronan allows versican to indirectly interact with the hyaluronan cell surface receptor CD44. The aim of this work was to study the effect of silencing the large versican isoforms (V0 and V1) and CD44 in the SK-mel-131 human melanoma c...

We identified a specific interaction between two secreted proteins, thrombospondin-1 and versican, that is induced during a toll-like receptor-3-dependent inflammatory response in vascular smooth muscle cells. Thrombospondin-1 binding to versican is modulated by divalent cations. This interaction is mediated by interaction of the G1 domain of versican with the N-module of thrombospondin-1 but o...