PERCOLL DENSITY GRADIENT CENTRIFUGATION OF RAT PITUITARY-TUMOR CELLS - A STUDY OF FUNCTIONAL-HETEROGENEITY WITHIN AND BETWEEN TUMORS WITH RESPECT TO GROWTH-RATES, PROLACTIN PRODUCTION AND RESPONSIVENESS TO THE SOMATOSTATIN ANALOG SMS 201-995

Tumor cells prepared from PRL-secreting rat pituitary 7315b tumors of increasing weight were separated on continuous Percoll density gradients, according to differences in their density. Whether the cell subpopulations obtained by density gradient separation showed differences in protein content per cell, PRL production per cell, growth rates and responsiveness to the somatostatin analog SMS 201-995 in vitro was investigated. In addition, we studied PRL release by individual 7315b tumor cells, using the reverse hemolytic plaque assay (RHPA). The tumor cells from tumors of increasing weight were recovered within a narrow density range (1.060-1.070 g/ml) and showed a normal distribution profile. There were no differences between the subpopulations with respect to the parameters mentioned above. Moreover, no differences were found with respect to these parameters between tumor cells derived from tumors of increasing weight. In agreement with the above data we found no evidence for subtypes of adenoma cells being preferentially responsive to SMS 201-995, using the RHPA. Conclusions: (1) the transplantable PRL-secreting rat pituitary tumor 7315b consists of a functionally homogeneous cell population; (2) growth of this tumor in vivo does not lead to the induction of functionally heterogeneous cell subpopulations within this tumor; (3) the escape of this tumor from the tumor growth-inhibitory effect of SMS 201-995, which has previously been demonstrated in vivo, may not have been the result of clonal selection of somatostatin-unresponsive cells. © 1990.