Lineage relationship between LNCaP and LNCaP-derived prostate cancer cell lines

BACKGROUND: LNCaP and its derivative cell lines, which include C4-2 (and the related C4-2B) and CL1, are used as models of prostate cancer. Unlike LNCaP, the other cell lines show features of progressed disease such as metastatic capability and hormone independence. Analyses were done to determine if C4-2 or CL1 cells were selected from pre-existent subpopulations in LNCaP. METHODS: Prostate cancer cells were characterized by cluster designation (CD) phenotyping. Specific cell populations were sorted by flow cytometry. DNA array analysis was used to probe differential gene expression. RESULTS: CD phenotyping showed that CL1 and C4-2 (and C4-2B) were very dissimilar, and C4-2 was more similar to LNCaP. One common difference between LNCaP and its derivatives was CD26, in which virtually all C4-2 or CL1 cells were CD26(+) but only approximately 10% of LNCaP cells were CD26(+). The CD26(+) subpopulation of LNCaP was isolated and cultured in vitro. After culture, a high percentage of the cells (descended from the sorted cells) were CD26(+), in contrast to those sorted by CD13 or CD44. The cultured CD13 and CD44 populations did not show a high percentage of CD13(+) and CD44(+) cells, respectively. CD13 and CD44 are markers, in addition to CD26, for CL1 but not for C4-2. CONCLUSIONS: C4-2 arose probably from CD26(+) LNCaP cells, while CL1 arose de novo.