Cell Surface Charge in Predicting Metastatic Potential of Aspirated Cells From the Dunning Rat Prostatic Adenocarcinoma Model

Abstract

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 106 tumor cells the H, G and AT-1 variants had <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 >90% metastases). Electrophoretic mobility expressed in μ/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 C.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 >-20.5 mV) was 80% and the predictive value of a negative test (value <-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.