HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells

Abstract

Abstract. Several studies have suggested that increased production of hyaluronan (HA) is associated with metastatic behavior in various malignant tumors. To our knowledge, HA molecular weights required for metastasis are still unsolved in osteosarcoma. We examined the size of HA and hyaluronan synthase (HAS) isoforms related to biological functions required for metastasis in the LM8 stably highly metastatic osteosarcoma cell line. We found that HA of molecular weight which HAS3 produces enhanced biological functions related to metastasis such as cell proliferation, invasion, and degradation of extracellular matrix. Moreover, cell proliferation and invasion were inhibited by suppressing the activity of HAS3 expressed in LM8 cells, using hyaluronan synthase suppressor, 4-methylumbelliferone (MU). HA with the molecular weight related to HAS2 was the most adherent to CD44 in LM8 cells, suggesting that HAS2 may play an important role in pericellular coat formation. These results suggest that HAS3-related HA enhances crucial biological activities necessary for metastasis and that HAS2-related HA offers an advantageous environment for osteosarcoma cells.

A Role for Versican in the Development of Leiomyosarcoma

“…Data from the overexpression of HAS1-3 or perturbation of hyaluronan production in several cancer cell lines have suggested that the accumulation of hyaluronan stimulates growth, survival, invasion, and metastasis of cancer cells (66 -68). Thus, it is likely that both hyaluronan and versican participate in the formation of a permissive microenvironment around the LMS tumor cells to promote their proliferation (42,69). It is interesting to note that our data show that a maximal proliferative response is achieved when the two molecules are added together, suggesting that a versican-hyaluronan complex may be optimal for the proliferative response of the LMS cells.…”

Hyaluronan Stabilizes Focal Adhesions, Filopodia, and the Proliferative Phenotype in Esophageal Squamous Carcinoma Cells

“…Using H-ras-transformed C3 fibroblasts, Hall et al (1994) demonstrated that HA leads to FAK tyrosine phosphorylation and augmented the formation of focal adhesions (36). Furthermore, in osteosarcoma cells, HA stimulates the phosphorylation of FAK and ERK1/2 (20). Despite the previously observed link between CD44 and FAK activation (37)(38), CD44 blocking antibodies had no influence on FAK degradation in ESCC.…”

Synthesis of hyaluronan in oesophageal cancer cells is uncoupled from the prostaglandin–cAMP pathway

“…showed that metastasis‐associated properties of cancer cells such as invasion and proliferation are enhanced by lower molecular weight forms of HA that are characteristic of HAS3 activity (Itano and Kimata, 2002). In contrast, HAS2 is believed to deliver higher molecular weight HA that supports pericellular coat formation and thus inhibits a malignant tumour cell phenotype (Tofuku et al. , 2006) unless it is further processed by for example hyaluronidases (Stern, 2008).…”