Background: Hyaluronan (HA) modulates key cancer cell functions through interaction with its CD44 and RHAMM receptors. Results: Low molecular weight HA (LMWHA) significantly increased (p Յ 0.01) the adhesion capacity of HT1080 cells in a RHAMM-dependent manner. Conclusion: RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways. Significance: Identification of a novel HA-signaling pathway.

The role of inflammation in the development of cancer was described as early as the nineteenth century. Abundant evidence supports the preposition that various cancers are triggered by infection and chronic inflammatory disease whereas, evading immune destruction has been proposed as one of the new “hallmarks of cancer.” Changes of the tumor microenvironment have been closely correlated to cancer-mediated inflammation. Hyaluronan (HA), an important extracellular matrices component, has become recognized as an active participant in inflammatory, angiogenic, fibrotic, and cancer promoting processes. This review discusses how HA and specific HA-binding proteins participate in and regulate cancer-related inflammatory processes.

Osteosarcoma is the most common primary bone tumour associated with childhood and adolescence. The possible role of the small leucine‐rich proteoglycan, lumican, in the growth and metastasis of various cancer types has recently been investigated. In this study, the expression of lumican was examined in moderately differentiated (MG‐63) and well‐differentiated (Saos 2) human osteosarcoma cell lines of high and low metastatic capability, respectively. Real‐time PCR, western blotting with antibodies against the protein core and keratan sulfate, and specific enzymatic digestions were the methods employed. The two human osteosarcoma cell lines were found to express and secrete lumican partly substituted with keratan sulfate glycosaminoglycans. Importantly, the non‐metastatic, well‐differentiated Saos 2 cells produced lumican at rates that were up to sevenfold higher than those of highly metastatic MG‐63 cells. The utilization of short interfering RNA specific for the lumican gene resulted in efficient down‐regulation of its mRNA levels in both cell lines. The growth of Saos 2 cells was inhibited by lumican, whereas their migration and chemotactic response to fibronectin were found to be promoted. Lumican expression was negatively correlated with the basal level of Smad 2 activation in these cells, suggesting that lumican may affect the bioavailability of Smad 2 activators. By contrast, these cellular functions of highly aggressive MG‐63 cells were demonstrated not to be sensitive to a decrease in their low endogenous lumican levels. These results suggest that lumican expression may be positively correlated with the differentiation and negatively correlated with the progression of osteosarcoma.

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Estrogens are related with the growth and development of target tissues and play a critical role in breast cancer progression. The effects of estrogens are mediated by the estrogen receptors ERa and ERb, which are members of the nuclear steroid receptor superfamily. To date, it is not known how these hormones elicit many of their effects on extracellular matrix molecules and how these effects can be connected with ER expression. For this purpose, the effect of estradiol on ER expression as well as on proteoglycan and metalloproteinase expression was studied. The effect of E2 on extracellular matrix molecule expression has been studied using ERa suppression in breast cancer cells. Our studies using ERa-positive MCF-7 cells show that estradiol affects the expression of syndecan-2, but not of syndecan-4, through ERa. Furthermore, the ability of estradiol to affect MMP-9 and TIMP-1 expression is connected with ERa status. Together, these data demonstrate the significant role of ERa on mediating the effect of estradiol on extracellular matrix molecules.