구.추천논문
- 조회4,929
Abstract
Minah Kim1,2, Young Jun Koh1,3, Kyung Eun Kim1,4, Bong Ihn Koh1,2, Do-Hyun Nam5, Kari Alitalo6, Injune Kim1,3, and Gou Young Koh1,2,3,4,5
Authors' Affiliations:1National Research Laboratory of Vascular Biology and Stem Cells, Departments of 2Biological Sciences, 3Graduate School of Medical Science and Engineering; 4Graduate School of Nanoscience and Technology (WCU), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, and 5Institute for Refractory Cancer Research Program, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; and 6Molecular/Cancer Biology Laboratory and Haartman Institute, University of Helsinki, FI-00014, Helsinki, Finland
Corresponding Author:
Gou Young Koh, Department of Graduate School of Medical Science and Engineering, KAIST, 373-1, Guseong-dong, Daejeon, 305-701, Korea. Phone: 82-42-350-2638, Fax: 82-42-350-2610.
Abstract
Highly metastatic and chemotherapy-resistant properties of malignant melanomas stand as challenging barriers to successful treatment; yet, the mechanisms responsible for their aggressive characteristics are not fully defined. We show that a distinct population expressing CD133 (Prominin-1), which is highly enriched after administration of a chemotherapeutic drug, dacarbazine, has enhanced metastatic potential in vivo. CD133+ tumor cells are located close to tumor-associated lymphatic vessels in metastatic organs such as the regional lymph nodes and lung. Lymphatic endothelial cells promote the migratory activity of a CD133+ subset to target organs and regulation of lymphatic growth efficiently modulates the metastasis of CD133+ tumor cells. We found that lymphatic vessels in metastatic tissues stimulate chemokine receptor 4 (CXCR4)+/CD133+ cell metastasis to target organs by secretion of stromal cell-derived factor-1 (SDF-1). The CXCR4+/CD133+ cells exhibited higher metastatic activity compared with CXCR4-/CD133+ cells and, importantly, blockade of CXCR4 coupled with dacarbazine efficiently inhibited both tumor growth and metastasis; dacarbazine alone could not attenuate tumor metastasis. The current study demonstrates a previously unidentified role of the lymphatic microenvironment in facilitating metastasis of chemoresistant melanoma cells via a specific chemotactic axis, SDF-1/CXCR4. Our findings suggest that targeting the SDF-1/CXCR4 axis in addition to dacarbazine treatment could therapeutically block chemoresistant CD133+ cell metastasis toward a lymphatic metastatic niche. Cancer Res; 70(24); 10411-21. ⓒ2010 AACR.
Footnotes
Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
논문정보
- Research article
- 2010년 12월 (BRIC 등록일 )
- 국내(교신)+국외 연구진
- 의약학 > 재생의학
- 구・추천논문
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