ABSTRACT
BACKGROUND: Pancreatic cancer is one of the most deadly malignancies with insufficient therapeutic options and poor outcome. Cancer stem cells (CSCs) are thought to be responsible for progression and therapy resistance. We investigated the potential of pancreatic cell lines for CSC research by analyzing to what extent they contain CSC populations and how representative these are compared to clinical tissue. METHODS: Six pancreatic cancer cell lines were analyzed by flow cytometry for CD326, CD133, CD44, CD24, CXCR4 and ABCG2. Subsequently, 70 primary pancreatic tissues were evaluated for CD326, CD133 and CD44 by immunohistochemistry. RESULTS: All the cell lines but one showed a stable expression pattern throughout biological replicates. Marker expression in clinical tissue of CD44 distinguished normal patients from pancreatic carcinoma patients with a sensitivity of 50% at 80% specificity and metastasized from nonmetastasized carcinomas with 69% sensitivity at 100% specificity. CONCLUSIONS: Our results indicate a link between elevated CD44 expression, malignancy and metastasis of pancreatic tissue. Furthermore, individual pancreatic cell lines show a substantial amount of cells with CSC properties which is comparable with interpatient variability detected in primary tissue. These pancreatic cancer cell lines could thus serve for urgently needed pharmacological CSC in vitro research.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma/metabolism , Cell Line, Tumor/metabolism , Neoplastic Stem Cells/metabolism , Pancreatic Neoplasms/metabolism , Aged , Aged, 80 and over , Carcinoma/pathology , Case-Control Studies , Female , Flow Cytometry , Humans , Male , Middle Aged , Pancreas/pathology , Pancreatic Neoplasms/pathologyABSTRACT
Volumes of flow sorted nuclei were analyzed from two highly endopolyploid (diploids with endopolyploid tissues) species (Arabidopsis thaliana and Barbarea stricta), from a less endopolyploid species (Allium cepa) and from two non-endopolyploid species (Chrysanthemum multicolor and Fritillaria uva-vulpis). Intraspecific as well as interspecific comparisons revealed a highly positive correlation (r > 0.99) between DNA content and nuclear volume. No significant differences between expected and measured nuclear volumes were noted indicating that chromatin packing is not increased with increasing DNA content in the tested plant species. In epidermis cells of A. thaliana, A. cepa and Ch. multicolor, a lower (r between 0.6 and 0.7) but significant positive correlation between nuclear volume and cell volume was found. This correlation is compatible with the hypothesis that endopolyploidization (EP = consecutive replication cycles not separated by nuclear and cell divisions) might speed up the growth of endopolyploid species and compensate for small genome size.
