期刊
ONCOTARGET
卷 8, 期 63, 页码 106296-106310出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.22435
关键词
NCAN; CSPG; neuroblastoma; tumor sphere
资金
- Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development [16ck0106011h0003]
- Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) [15k15079, 24590377]
- CREST program, Japan Science and Technology Agency [E15656320]
- Grants-in-Aid for Scientific Research [15K15079, 16K08617, 15K18442, 17K10131, 24590377] Funding Source: KAKEN
Neurocan (NCAN), a secreted chondroitin sulfate proteoglycan, is one of the major inhibitory molecules for axon regeneration in nervous injury. However, its role in cancer is not clear. Here we observed that high NCAN expression was closely associated with the unfavorable outcome of neuroblastoma (NB). NCAN was also highly and ubiquitously expressed in the early lesions and terminal tumor of TH-MYCN mice, a NB model. Interestingly, exogenous NCAN (i.e., overexpression, recombinant protein and conditioned medium) transformed adherent NB cells into spheres whose malignancies in vitro (anchorage-independent growth and chemoresistance) and in vivo (xenograft tumor growth) were potentiated. Both chondroitin sulfate sugar chains and NCAN's core protein were essential for the sphere formation. The CSG3 domain was essential in the moiety of NCAN. Our comprehensive microarray analysis and RT-qPCR of mRNA expression suggested that NCAN treatment promoted cell division, and urged cells to undifferentiated state. The knockdown of NCAN in tumor sphere cells cultured from TH-MYCN mice resulted in growth suppression in vitro and in vivo. Our findings suggest that NCAN, which stimulates NB cells to promote malignant phenotypes, is an extracellular molecule providing a growth advantage to cancer cells.
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