Cell surface charge in predicting metastatic potential of aspirated cells from the Dunning rat prostatic adenocarcinoma model.

The transplantable Dunning R-3327 rat prostatic adenocarcinoma model has provided a series of tumor variants with broad ranges of metastatic potential. We tested whether cell surface charge might be related to metastatic potential by measuring the electrophoretic mobility of live tumor cells obtained by needle aspiration. Cells were aspirated from tumors with low metastatic potential (following subcutaneous inoculation of 10(6) tumor cells the H, G and AT-1 variants had less than 5% metastases; AT-2 had 5-20%) and were compared to the electrophoretic mobility of cells aspirated from highly metastatic tumors (MAT-LyLu, MAT-Lu, AT-3 had greater than 90% metastases). Electrophoretic mobility expressed in mu/sec/volt/cm. was measured on 100 cells from each tumor subline, and the cell surface charge expressed as a zeta potential was calculated from electrophoretic mobility using the Helmholtz-Smoluchowski equation. The average zeta potential (+/- S.E.M.) for the four sublines with low metastatic potential was (-17.4 +/- 0.4 mV) compared to the three sublines with high metastatic potential (-26.5 +/- 0.7 mV), and the differences were significant (p less than .01) using the Mann-Whitney Wilcoxon test. Using a zeta potential of -20.5 mV as the cutoff between high and low metastatic potential, the sensitivity and specificity of zeta potential in predicting metastatic potential in 140 determinations on seven tumor lines were 92% and 82.5%, respectively. The predictive value of a positive test (value greater than -20.5 mV) was 80% and the predictive value of a negative test (value less than -20.5 mV) was 93%. The results support a difference in the cell surface charge between these metastatic and nonmetastatic tumors with increasing negativity at the cell surface correlating with increased metastatic potential, but not with tumor growth rates.

[1]  H. Bosmann,et al.  Biochemical Parameters correlated with Tumour Cell Implantation , 1973, Nature.

[2]  E. Mayhew,et al.  Ribonucleic acid at the periphery of different cell types, and effect of growth rate on ionogenic groups in the periphery of cultured cells. , 1968, Experimental cell research.

[3]  A. Partin,et al.  Time lapse videomicroscopic identification of Dunning R-3327 adenocarcinoma and normal rat prostate cells. , 1987, The Journal of urology.

[4]  G. Seaman,et al.  PHYSICOCHEMICAL DIFFERENCES BETWEEN ASCITIC AND SOLID FORMS OF SARCOMA 37 CELLS. , 1963, Cancer research.

[5]  William B. Isaacs,et al.  Establishment and characterization of seven dunning rat prostatic cancer cell lines and their use in developing methods for predicting metastatic abilities of prostatic cancers , 1986 .

[6]  I. Zeidman.  Metastasis: a review of recent advances. , 1957, Cancer research.

[7]  V. Dubowitz.  Enzymatic Maturation of Skeletal Muscle , 1963, Nature.

[8]  Vassar Ps.  THE ELECTRIC CHARGE DENSITY OF HUMAN TUMOR CELL SURFACES. , 1963 .

[9]  E. Mayhew,et al.  Ribonuclease‐susceptible charged groups at the surface of ehrlich ascites tumour cells , 1969, International journal of cancer.

[10]  G. Seaman,et al.  ELECTROPHORETIC STUDIES ON SOME TYPES OF MAMMALIAN TISSUE CELL. , 1964, Cancer research.

[11]  L. Sinks,et al.  The elekctrokinetic surfaces of human cells of lymphoid origin and their ribonuclease susceptibility. , 1970, Cancer research.

[12]  P. Emmelot,et al.  Increased sialic acid density in surface glycoprotein of transformed and malignant cells--a general phenomenon? , 1973, Cancer research.

[13]  E. J. Ambrose,et al.  Differences between the Electrical Charge carried by Normal and Homologous Tumour Cells , 1956, Nature.

[14]  M. van Vliet,et al.  Electrophoretic mobility properties of murine hemopoietic cells in different stages of development. , 1981, Experimental Hematology.

[15]  R. Pethig,et al.  Changes in cell surface charge and transmembrane potential accompanying neoplastic transformation of rat kidney cells. , 1987, Biochimica et biophysica acta.

[16]  A. Bangham,et al.  An Apparatus for Microelectrophoresis of Small Particles , 1958, Nature.

[17]  G. Seaman,et al.  The electrokinetic characterization of the Ehrlich ascites carcinoma cell. , 1962, Experimental cell research.

[18]  Aaron W. Miller,et al.  Sialic Acid Content of the Erythrocyte and of an Ascites Tumor Cell of the Mouse , 1963 .

[19]  G. Seaman,et al.  Sialic Acids and the Electrokinetic Charge of the Human Erythrocyte , 1961, Nature.

[20]  E. J. Ambrose,et al.  A Correlation between Electrical Surface Charge and Some Biological Characteristics During the Stepwise Progression of a Mouse Sarcoma , 1958, Nature.

[21]  S. Ben-Or,et al.  Electrophoretic Mobilities of Normal and Regenerating Liver Cells , 1960, Nature.

[22]  C. Buck,et al.  The surface glycoproteins of a mouse melanoma growing in culture and as a solid tumor in vivo. , 1975, Cancer research.

[23]  T. Hauschka,et al.  Malignancy, electrophoretic mobilities and sialic acids at the electrokinetic surface of TA3 cells , 1970, International Journal of Cancer.

[24]  G. Seaman,et al.  Electrophoretic Mobility of Cultured Mesodermal Tissue Cells , 1961, Nature.

[25]  E. Mayhew.  Cellular Electrophoretic Mobility and the Mitotic Cycle , 1966, The Journal of general physiology.

[26]  P. Vassar.  Electrophoretic Mobility of Human Tumour Cells , 1963, Nature.

[27]  A. Partin,et al.  Prediction of metastatic potential by a new grading system of cell motility: validation in the Dunning R-3327 prostatic adenocarcinoma model. , 1987, The Journal of urology.

[28]  M. Bretscher,et al.  How animal cells move. , 1987, Scientific American.