The CD49d(+/high) subpopulation from isolated human breast sarcoma spheres possesses tumor-initiating abilityopen access
- Authors
- Lee, Kyung-Min; Han, Wonshik; Kim, Jong Bin; Shin, Incheol; Ko, Eunyoung; Park, In Ae; Lee, Dong Sup; Oh, Kuenhee; Noh, Dung-Young
- Issue Date
- Mar-2012
- Publisher
- SPANDIDOS PUBL LTD
- Keywords
- tumor-initiating cells; breast sarcoma; CD49d
- Citation
- INTERNATIONAL JOURNAL OF ONCOLOGY, v.40, no.3, pp.665 - 672
- Indexed
- SCIE
SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF ONCOLOGY
- Volume
- 40
- Number
- 3
- Start Page
- 665
- End Page
- 672
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/166114
- DOI
- 10.3892/ijo.2011.1289
- ISSN
- 1019-6439
- Abstract
- Primary breast sarcomas (PBSs) that arise from mammary stroma are very rare, highly aggressive and therapy-resistant tumors with a heterogeneous phenotype. In this study, we sought to identify tumor-initiating cells (TICs) in PBSs and to describe their features. We isolated long-term self-renewing sarcospheres (designated NDY-1) from primary breast carcinosarcoma tissue (sarcoma component >95%) using the anchorage-independent culture method. NDY-1 spheres expressed various mesenchymal cell markers, and their tumorigenic potential was markedly reduced in adherent culture conditions, compared to spheres. Screening for integrins revealed a marked decrease in CD49d expression in adherent culture conditions of NDY-1. The CD49d(+/high) subpopulation sorted from NDY-1 spheres displayed higher cell viability and sphere-forming ability than CD49d(-/low) population in vitro. Moreover, the CD49d(+/high) population displayed high tumor initiating ability in limiting dilution transplantation to NOD/SCID mice, and the xenotransplanted CD49d(+/high) population recapitulated the complexity of the original primary tumors. Greater doxorubicin resistance was exhibited by the CD49d(+/high) population, compared with the CD49d(-/low) population. Thus, our results collectively demonstrate that CD49d(+/high) cells from sarcospheres display enhanced sphere-forming, drug resistance and tumor-initiating abilities. To our knowledge, this is the first study to identify TICs from breast sarcoma.
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