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Cancer cell invasion comprises steps in the destruction of the basement membrane and migration of cells into the connective tissue. These cells further migrate into lymph ducts and small vessels to reach metastasis. The extracellular matrix (ECM) provides a microenvironment for cells, and its destruction is associated with cancer cell invasion. Among matrix metalloproteinases (MMPs), both MMP-2 and 9 digest type IV collagen, a major component of the basement membrane, and MMP-14/MT1-MMP, a membrane-type MMP, activates MMP-2. Thus, these MMPs play a central role in cancer cell invasion. MMPs also cleave latent forms of growth factors and signaling molecules, releasing and activating them, which influence neo-vascularization and cancer apoptosis. Like proteins, carbohydrates are known to be involved in cancer invasion. Hyaluronan is known to both stimulate and inhibit cancer invasion, depending on its molecular size. Heparanase, which digests heparan sulfate, is known to facilitate cancer invasion and metastasis. In summary, ECM provides a microenvironment that regulates cell behavior and its structure altered by MMPs affects cancer cell invasion.

A 63-year-old woman was diagnosed as having multiple myeloma (MM), IgG-kappa type, stage IIIA, in October 2003. She achieved partial response after receiving three courses of VAD therapy and one course of high dose dexamethasone therapy (HDD); maintenance therapy consisted of melphalan and prednisolone. In November 2004, the patient developed spinal canal stenosis that required surgery. At the end of December 2004, the patient developed renal dysfunction that progressed to anuria. A CT scan showed multiple retroperitoneal masses that impinged on and obstructed both ureters and caused bilateral hydronephroses. Renal function improved after a right percutaneous nephrostomy and chemotherapy consisting of HDD, cyclophosphamide, vincristine, and doxorubicin. Nevertheless, the patient died due to MM in February 2005. On autopsy, multiple retroperitoneal and pelvic plasmacytomas with 13q- and t(4;14) (p16;q32) were found. Our patient is a rare case that, in the terminal stage of MM, developed aggressive phase multiple myeloma with extramedullary plasmacytomas that caused acute renal failure due to compression on both ureters.

Proteoglycans are a family of glycoconjugates consisting of central core proteins with covalently attached glycosaminoglycan (GAG) side chains. Several proteoglycans participate in the development and maintenance of cartilage. Versican/PG-M positively regulates the formation of the mesenchymal matrix during the mesenchymal cell condensation, an essential process of chondrogenesis. Aggrecan, major proteoglycan in cartilage, forms the proteoglycan aggregate with hyaluronan and link protein. The aggregates provide cartilage with a gel-like property and resistant capacity to mechanical load through water absorption. Degradation of aggrecan by aggrecanases and matrix metalloproteinases leads to the cartilage degeneration.

The proteoglycan aggregate is the major structural component of the extracellular matrix of the cartilage, composed of aggrecan, hyaluronan (HA) and link protein (LP). The aggregates provide cartilage with unique gel-like property and resistance to deformation through water absorption. Natural knockout mice of aggrecan, termed cartilage matrix deficiency, and LP-null mice exhibit decreased levels of aggrecan depositon in cartilage and correspond well with their phenotypes such as dwarfism and spinal misalignment, demonstrating in vivo roles of the aggregate in cartilage development and homeostasis. Our recent studies demonstrate that versican/PG-M, another member of aggrecan family with a similar domain structure, binds both HA and LP, forming an aggregate. Further functional analyses of domains and subdomains showed distinct interaction of versican/PG-M with LP from aggrecan, suggesting that the versican/PG-M aggregate may have different function in cartilage.