THE EFFECT OF DIBUTYRYL CAMP (DBCAMP) ON MORPHOLOGICAL-DIFFERENTIATION, GROWTH AND INVASION INVITRO OF A HAMSTER BRAIN-TUMOR CELL-LINE - A COMPARATIVE-STUDY OF DBCAMP EFFECTS IN 2-DIMENSIONAL AND 3-DIMENSIONAL CULTURES

The use of agents that stimulate cancer cells to differentiate is proposed as a potential approach to the treatment of malignancy. To evaluate the effects of a differentiation inducer on morphology, growth and invasion in vitro of brain-tumor cells, a diffusely invasive hamster glial cell line (CxT3C15) was treated with 1 mM dibutyryl cyclic adenosine monophosphate (dBcAMP). The efficacy of dBcAMP was tested in monolayer cultures, 3-dimensional static cultures (i.e., spheroids) and confrontation cultures with an embryonic chick heart. CxT3C15 cells exhibited increased numbers of long cellular processes (morphological differentiation) following treatment of monolayer cultures with 1 mM dBcAMP. One mM dBcAMP also altered the macroscopic and ultrastructural morphology of CxT3C15 grown as spheroids. These alterations were: (i) a fast transition of rough to smooth morphology macroscopically, and (ii) fading of the cell borders concomitant with the disappearance of cell-membrane excrescences, as seen by scanning electron microscopy. Exponential growth of CxT3C15 in monolayers was not changed following treatment with 1 mM dBcAMP. Treatment of CxT3C15 spheroids with the same dose of dBcAMP caused a reduction of relative volume increase (30-40%). Invasion of CxT3C15 in an embryonic chick heart in vitro was not altered after addition (prior to or at the time of co-culture) of 1 mM dBcAMP to the co-cultures. These results indicate that invasion of CxT3C15 is not necessarily linked to morphological differentiation or moderated by reduced proliferation.