CONTROL OF NEUROBLASTOMA CELL-PROLIFERATION AND DIFFERENTIATION HLL HUMAN BONE-MARROW

BACKGROUND, Neuroblastoma (NB) is one of the few tumors known to under go spontaneous regression. Its progression, however, often leads to ba ne marrow (BM) metastasis. Proliferation and differentiation of human NB cells may be regulated in vitro by a variety of biologic agents, so me of which are released by low-density BM and peripheral blood (PB) c ells. Little is known regarding BM cell-derived control of NB cell gro wth and differentiation. METHODS. The proliferative and differentiativ e responses of NB cells, to BM cell-, and to PB cell-derived condition ed medium (CM) were evaluated in comparison to cytokine-induced respon ses. RESULTS. CM from unstimulated cultures of low density BM and PB c ells, from healthy donors, from newborn infants, and from NB patients, significantly and reproducibly stimulate NR cell growth in vitro. The intensity of CM-induced stimulation was not attained by recombinant h uman tumor necrosis factor (rhTNF), interferon (rhIFN), or granulocyte -monocyte colony stimulating factor (rhGM-CSF); and although epidermal growth factor (rhEGF) and transforming growth factor alpha (rhTGF alp ha) were strongly stimulatory, neutralizing antibodies against each of these agents did not affect CM-derived activity. in contrast to grow th stimulation, differentiation of CM-treated NB cells, was reproducib ly suppressed, as reflected in abrogation of neuronal cell morphology as well as of neurofilament and neuron specific enolase expression. CO NCLUSIONS. Spontaneous regression of NB tumors, on one hand and BM met astasis on tile other may be associated with the extent and nature of the NE cell response to regulatory activity released by BM and PB cell s. (C) 1996 American Cancer Society.