Hyaluronan (HA) has been shown to play crucial roles in the tumorigenicity of malignant
tumors.
Chondrosarcoma, particularly when low-grade, is characterized by the formation of an extracellular matrix (ECM) containing abundant HA, and its drug/radiation resistance has become a clinically relevant problem. This study aimed to evaluate the effects of a novel
hyaluronidase, KIAA1199, on ECM formation as well as antitumor effects on
chondrosarcoma. To clarify the roles of KIAA1199 in
chondrosarcoma, mouse KIAA1199 was stably transfected to Swarm rat
chondrosarcoma (RCS) cells (histologically grade 1). We investigated the effects of KIAA1199 on RCS cells in vitro and an autografted model in vivo. HA
binding protein (HABP) stainability and ECM formation in KIAA1199-RCS was markedly suppressed compared with that of control cells. No significant changes in
messenger RNA expression of Has1, Has2, Has3, Hyal1, or Hyal2 were observed. KIAA1199 expression did not affect proliferation or apoptosis but inhibited migration and invasion of RCS cells. In contrast, the expression of KIAA1199 significantly inhibited the growth of grafted
tumors and suppressed the stainability of
alcian blue in
tumor tissues. Although there was no direct inhibitory effect on proliferation in vitro, induction of KIAA1199 showed the antitumor effects in grafted
tumor growth in vivo possibly due to changes in the tumor microenvironment such as inhibition of ECM formation. Forced expression of KIAA1199 exhibits antitumor effects on low-grade
chondrosarcoma, which has chemo- and radio-
therapy resistant features. Together, KIAA1199 could be a novel promising therapeutic tool for low-grade
chondrosarcoma, mediated by the degradation of HA.