The University of Osaka · Medicine
Professor Masayuki Miyasaka's research lab focuses on the molecular mechanisms underlying tumor progression, with a central emphasis on the roles of extracellular matrix components—particularly hyaluronan (HA) and proteoglycans such as versican—in cancer cell migration, invasion, and metastasis. The lab investigates how specific fragments of HA and glycosaminoglycan (GAG) chains on proteoglycans modulate cell surface receptors like CD44 and influence chemokine signaling, thereby promoting tumor cell behavior. A key research direction involves understanding the proteolytic cleavage of adhesion molecules and the functional consequences of extracellular matrix remodeling in the tumor microenvironment. The lab also explores the interplay between extracellular matrix molecules and immune cell trafficking molecules, such as L-selectin and chemokines, to uncover novel mechanisms of cancer metastasis and potential therapeutic targets.
Figures are computed from collected data and may differ slightly.
CD44 is an adhesion molecule that serves as a cell surface receptor for several extracellular matrix components, including hyaluronan (HA). The proteolytic cleavage of CD44 from the cell surface plays a critical role in the migration of tumor cells. Although this cleavage can be induced by certain stimuli such as phorbol ester and anti-CD44 antibodies in vitro, the physiological inducer of CD44 cleavage in vivo is unknown. Here, we demonstrate that HA oligosaccharides of a specific size range in
We previously reported that versican, a large chondroitin sulfate proteoglycan, isolated from a renal adenocarcinoma cell line, ACHN, binds L-selectin. Here we report that versican also binds certain chemokines and regulates chemokine function. This binding was strongly inhibited by the chondroitinase digestion of versican or by the addition of soluble chondroitin sulfate (CS) B, CS E, or heparan sulfate. Furthermore, these glycosaminoglycans (GAGs) could bind directly to the chemokines that bin
Although chemokines have been thought of primarily as leukocyte attractants, a growing body of evidence indicates that they also contribute to a number of tumor-related processes, such as tumor cell growth, angiogenesis/angiostasis, local invasion, and metastasis. The current knowledge of the possible involvement of chemokines and their receptors in these cellular events are reviewed here. The operating mechanism of chemokines in relation to metastatic processes in vivo are also discussed.
Hyaluronan (HA) is an extracellular matrix glycosaminoglycan that interacts with cell-surface receptors, including CD44. Although HA usually exists as a high molecular mass polymer, HA of a much lower molecular mass that shows a variety of biological activities can be detected under certain pathological conditions, particularly in tumors. We previously reported that low molecular weight HAs (LMW-HAs) of a certain size range induce the proteolytic cleavage of CD44 from the surface of tumor cells
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