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Hierarchical Organization of Prostate Cancer Cells in Xenograft Tumors: The CD44⁺2ß1⁺ Cell Population Is Enriched in Tumor-Initiating Cells

¹ Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division, Smithville, Texas and ² Program in Environmental and Molecular Carcinogenesis, Graduate School of Biomedical Sciences, Houston, Texas

Requests for reprints: Dean G. Tang, Department of Carcinogenesis, Science Park-Research Division, The University of Texas M. D. Anderson Cancer Center, 1808 Park Road 1C, Smithville, TX 78957. Phone: 512-237-9575; Fax: 512-237-2475; E-mail: dtang{at}mdanderson.org.

Prostate cancer cells are heterogeneous in their tumorigenicity. For example, the side population cells isolated from LAPC9 xenografts are 100 to 1,000 times more tumorigenic than the corresponding non–side population cells. Highly purified CD44⁺ prostate cancer cells from several xenografts are also enriched in prostate cancer stem/progenitor cells. Because the CD44⁺ prostate cancer cell population is still heterogeneous, we wonder whether we could further enrich for tumorigenic prostate cancer cells in this population using other markers. Integrin 2ß1 has been proposed to mark a population of normal human prostate stem cells. Therefore, we first asked whether the 2ß1^+/hi cells in prostate tumors might also represent prostate cancer stem cells. Highly purified (98%) 2ß1^+/hi cells from three human xenograft tumors, Du145, LAPC4, and LAPC9, show higher clonal and clonogenic potential than the 2ß1^–/lo cells in vitro. However, when injected into the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse prostate or s.c., the 2ß1^+/hi prostate cancer cells are no more tumorigenic than the 2ß1^–/lo cells. Immunofluorescence studies reveal that CD44 and 2ß1 identify an overlapping and inclusive population of prostate cancer cells in that 70% of 2ß1^+/hi cells are CD44⁺ and 20% to 30% of CD44⁺ cells are distributed in the 2ß1^–/lo cell population. Subsequently, we sorted out CD44⁺2ß1^+/hi, CD44⁺2ß1^–/lo, CD44^–2ß1^+/hi, and CD44^–2ß1^–/lo cells from LAPC9 tumors and carried out tumorigenicity experiments. The results revealed a hierarchy in tumorigenic potential in the order of CD44⁺2ß1^+/hi CD44⁺2ß1^–/lo > CD44^–2ß1^+/hi >> CD44^–2ß1^–/lo. These observations together suggest that prostate cancer cells are organized as a hierarchy. [Cancer Res 2007;67(14):6796–805]

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				Correction: CD44, {alpha}2{beta}1, and Prostate Tumor Stem/Progenitors Cancer Res., September 15, 2007; 67(18): 8973 - 8973. [Full Text] [PDF]