|Budget Amount *help
¥6,100,000 (Direct Cost : ¥6,100,000)
Fiscal Year 1997 : ¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1996 : ¥4,200,000 (Direct Cost : ¥4,200,000)
To assess the possibility that cell differentiation plays an important role in spontaneous regression in neuroblastoma (NB), we analyzed origins of Schwannian cells and ganglionic cells within NB tissues using FISH and cytofluorometry. FISH analysis on AMeX-fixed tumor sections from a stage-1 patient showed that the Schwannian cells had two signals of chromosome 1 while the tumor cells had three. This discordance suggests that the Schwannian cells might not have derived from the tumor cells. On the other hand, cytofluorometry on a touch smear specimen from a stage-2 patient revealed that the ganglionic cells and the tumor cells were near-triploid. The consistency in DNA-content between them suggests that the ganglionic cells might have been differentiated from the tumor cells.
Furthermore, we studied whether midkine, a neurotrophic polypeptide, plays a role in neuronal differentiation in NB or not. A retinoic acid analogue, E5166, induces neuronal defferentiation morphologically in NB cell lines. To examine expression level of midkine during neuronal differentiation by E5166 treatment, we measured its level by Northern blot in two NB cell lines, SK-N-SH and KP-N-RTBM1. The expression level of midkine significantly elevated at days 1,2 and 3 (p<0.001) in SK-N-SH.In KP-N-RTBM1, midkine expression was also upregulated at days 1,2,3 and 7 even without statistical significance.
Our result suggests that NB cells could differentiate into ganglionic cells in vivo, and that midkine might play an important role in neuronal differentiation in NB.Further study concerning the neuronal differentiation in NB may provide clue to a better understanding of the spontaneous regression in NB.