TY - JOUR
T1 - Human tumor cell proliferation evaluated using Manganese-Enhanced MRI
AU - Braun, Rod D.
AU - Bissig, David
AU - North, Robert
AU - Vistisen, Kerry S.
AU - Berkowitz, Bruce A.
N1 - Funding Information:
The authors wish to thank Drs. Mary Hendrix and Karla Daniels for supplying the C918 cells, Dr. June Kan-Mitchell for providing the OCM-1 cells, and Dr. Lisa Anne Polin for supplying the PC-3 cells. The Microscopy, Imaging and Cytometry Resources Core is supported, in part, by NIH Center grant P30CA22453 to The Karmanos Cancer Institute, Wayne State University and the Perinatology Research Branch of the National Institutes of Child Health and Development, Wayne State University.
PY - 2012/2/17
Y1 - 2012/2/17
N2 - Background: Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn 2+ [measured with manganese-enhanced MRI (MEMRI)], is linked to proliferation rate in vitro. Methodology/Principal Findings: Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl 2 for one hour and then thoroughly washed. MEMRI R 1 values (longitudinal relaxation rates), which have a positive linear relationship with Mn 2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn 2+-induced increases in R 1 compared to cells not exposed to Mn 2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R 1 values and proliferation rate (p≤0.005), while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R 1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet. Conclusions/Significance: These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.
AB - Background: Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn 2+ [measured with manganese-enhanced MRI (MEMRI)], is linked to proliferation rate in vitro. Methodology/Principal Findings: Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl 2 for one hour and then thoroughly washed. MEMRI R 1 values (longitudinal relaxation rates), which have a positive linear relationship with Mn 2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn 2+-induced increases in R 1 compared to cells not exposed to Mn 2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R 1 values and proliferation rate (p≤0.005), while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R 1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet. Conclusions/Significance: These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.
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U2 - 10.1371/journal.pone.0030572
DO - 10.1371/journal.pone.0030572
M3 - Article
C2 - 22363447
AN - SCOPUS:84857170978
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 2
M1 - e30572
ER -