Skip to main content
NCBI home page
Cancer Science logoLink to Cancer Science
. 2005 Aug 19;94(1):37–42. doi: 10.1111/j.1349-7006.2003.tb01349.x

Malignant rhabdoid tumor shows a unique neural differentiation as distinct from neuroblastoma

Katsumi Higashino 1, Tsutomu Narita 1, Takashi Taga 1, Shigeru Ohta 1,2,✉, Yoshihiro Takeuchi 1
PMCID: PMC11160256  PMID: 12708472

Abstract

Malignant rhabdoid tumors (MRT) show a multiphenotypic diversity, including a neural phenotype. To elucidate the difference in neural characteristics between MRT and neuroblastoma, we examined the expression of synapsin I, neuron‐restrictive silencer factor (NRSF), neurofilament medium‐size (NF‐M) and chromogranin A (CGA) in five MRT cell lines (TM87–16, STM91–01, TTC549, TTC642 and YAM‐RTK1) and five neuroblastoma cell lines under differentiation‐induction with 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). Our results showed TM87–16 and TTC642 cells, expressed synapsin I and NF‐M before TPA induction, had a neural phenotype. After differentiation‐induction, only TM87–16 cells expressed CGA. Among all neuroblastoma cells, expression of NF‐M and CGA was stable at a high level throughout TPA‐induced differentiation. In TM87–16 and TTC642 MRT cells, synapsin I mRNA promptly increased after TPA differentiation, with the peak level at 6 h, and thereafter, synapsin I mRNA rapidly decreased in a time‐dependent manner. The decreased expression of synapsin I correlated with an increased expression of NRSF during differentiation‐induction. In contrast, in some neuroblastoma cells, a significant up‐regulation of synapsin I was observed concurrently with a down‐regulation of NRSF. The inverse relationship between NRSF and synapsin I expression in TM87–16 and TTC642 MRT cells was opposite to that of neuroblastoma cells. Our results showed that the neural characteristics of these MRT cells are fairly distinct from those of neuroblastoma cells. These MRT cells appeared to have only limited capability for neural differentiation, and were still in an extremely early stage of neural differentiation. (Cancer Sci 2003; 94: 37–42)

References

  • 1. Beckwith JB. Wilms' tumor and other renal tumors of childhood: a selective review from the National Wilms' Tumor Study Pathology Center. Hum Pathol 1983; 14: 481–92. [DOI] [PubMed] [Google Scholar]
  • 2. Beckwith JB, Palmer NF. Histopathology and prognosis of Wilm's tumor: results from the First National Wilm's Tumor Study. Cancer 1999; 41: 1937–48. [DOI] [PubMed] [Google Scholar]
  • 3. Haas JE, Palmer NF, Weinberg AG, Beckwith JB. Ultrastructure of malignant rhabdoid tumor of the kidney: a distinctive renal tumor of children. Hum. Pathol 1981; 12: 646–57. [DOI] [PubMed] [Google Scholar]
  • 4. Ota S, Crabbe DC, Tran TN, Shimada H. Malignant rhabdoid tumor: a study with two established cell lines. Cancer 1993; 71: 2862–72. [DOI] [PubMed] [Google Scholar]
  • 5. Kaiserling E, Ruck P, Handgretinger R, Leipoldt M, Hipfel R. Immunohistochemical and cytogenic findings in malignant rhabdoid tumor. Gen Diagn Pathol 1996; 141: 327–37. [PubMed] [Google Scholar]
  • 6. Giangaspero F, Zanetti G, Mancini A. Sarcomatous variant of Wilm's tumor: a light and immunohistochemical study of four cases. Turnori 1981; 67: 367–73. [DOI] [PubMed] [Google Scholar]
  • 7. Tsokos M, Kouraklis G, Chandra RS, Bhagavan BS, Triche TJ. Malignant rhabdoid tumor of the kidney and soft tissues: evidence for a diverse morphological and immunocytochemical phenotype. Arch Pathol Lab Med 1989; 113: 115–20. [PubMed] [Google Scholar]
  • 8. Gonzalez‐Crussi F, Goldschmidt RA, Hsueh W, Trujillo YP. Infantile sarcoma with intracytoplasmic filamentous inclusions: distinctive tumor of possible histiocytic origin. Cancer 1982; 49: 2365–75. [DOI] [PubMed] [Google Scholar]
  • 9. Bonnin JM, Rubinstein L, Palmer NF, Beckwith JB. The association of embryonal tumors originating in the kidney and in the brain: a report of seven cases. Cancer 1984; 54: 2137–46. [DOI] [PubMed] [Google Scholar]
  • 10. Kinoshita Y, Tamiya S, Oda Y, Mimori K, Inoue H, Ohta S, Tajiri T, Suita S, Tsuneyoshi M. Establishment and characterization of malignant rhabdoid tumor of the kidney. Oncol Rep 2001; 8: 43–8. [PubMed] [Google Scholar]
  • 11. Parham DM, Peiper SC, Robicheaux G. Malignant rhabdoid tumor of the liver: evidence for epithelial differentiation. Arch Pathol Lab Med 1988; 112: 61–4. [PubMed] [Google Scholar]
  • 12. Sugimoto T, Hosoi H, Horii Y, Ishida H, Mine H, Takahashi K, Abe T, Ohta S, Sawada T. Malignant rhabdoidtumor cell lines showing neural and smooth‐muscle‐cell phenotype. Int J Cancer 1999; 82: 678–86. [DOI] [PubMed] [Google Scholar]
  • 13. Gansler T, Gerald W, Anderson G, Gramling TS, Williams CH, Sens D, Garvin AJ. Characterization of a cell line derived from rhabdoid tumor of kidney. Hum Pathol 1991; 22: 259–66. [DOI] [PubMed] [Google Scholar]
  • 14. Handgretinger R, Kimmig A, Koscielank E, Schmidt D, Rudolpha G, Wolburg H, Paulus W, Schilbach‐Stueckle K, Ottenlinger C, Menrad A, Sproll M, Bruchelt G, Dopfer R, Treuner J, Niethammer D. Establishment and characterization of a cell line (Wa‐2) derived from an extrarenal rhabdoid tumor. Cancer Res 1990; 50: 2177–82. [PubMed] [Google Scholar]
  • 15. Parham DM, Weeks DA, Beckwith JB. The clinicopathologic spectrum of putative extrarenal rhabdoid tumors. An analysis of 42 cases studied with immunohistochemistry or electron microscopy. Am J Surg Pathol 1994; 18: 1010–29. [DOI] [PubMed] [Google Scholar]
  • 16. Suzuki A, Ohta S, Shimada M. Gene expression of malignant tumor cell lines by reverse transcriptase‐polymerase chain reaction. Diagn Mol Pathol 1998; 6(6): 326–32. [DOI] [PubMed] [Google Scholar]
  • 17. Yoshida S, Narita T, Taga T, Ohta S, Takeuchi Y. Malignant rhabdoid tumor shows incomplete neural characteristics as revealed by expression of SNARE complex. J Neurosci Res 2002; 69: 642–52. [DOI] [PubMed] [Google Scholar]
  • 18. Narita T, Taga T, Sugita K, Nakazawa S, Ohta S. The autocrine loop of epidermal growth factor receptor‐epidermal growth factor/ transforming growth factor‐αt in malignant rhabdoid tumor cell lines: heterogeneity of autocrine mechanism in TTC549. Jpn J Cancer Res 2001; 92: 269–78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Chong JA, Tapia‐Ramirez J, Kim S, Toledo‐Aral JJ, Zheng Y, Boutros MC, Altshuller YM, Frohman MA, Kraner SD, Mandel G. REST: a mammalian silencer protein that restricts sodium channel gene expression to neurons. Cell 1995; 80: 949–57. [DOI] [PubMed] [Google Scholar]
  • 20. Schoenherr CJ, Anderson DJ. The neuron‐restrictive silencer factor (NRSF): a coordinate represser of multiple neuron‐specific genes. Science 1995; 267: 1360–3. [DOI] [PubMed] [Google Scholar]
  • 21. Schoenherr CJ, Paquette AJ, Anderson DJ. Identification of potential target genes for the neuron‐restrictive silencer factor. Proc Natl Acad Sci USA 1996; 32: 9881–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22. Li L, Suzuki T, Mori N, Greengard P. Identification of a functional silencer element involved in neuron‐specific expression of the synapsin I gene. Proc Natl Acad Sci USA 1993; 90: 1460–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Schoch S, Cibelli G, Thiel G. Neuron‐specific gene expression of synapsin I. Major role of a negative regulatory mechanism. J Biol Chem 1996; 271: 3317–23. [DOI] [PubMed] [Google Scholar]
  • 24. Thiel G, Lietz M, Cramer M. Biological activity and modular structure of RE‐1‐silencing transcription factor (REST), a represser of neuronal genes. J Biol Chem. 1998; 273: 26891–9. [DOI] [PubMed] [Google Scholar]
  • 25. Chin L‐S, Li L, Ferreira A, Kosik KS, Greengard P. Impairment of axonal development and of synaptogenesis in hippocampal neurons of synapsin‐I deficient mice. Proc Natl Acad Sci USA 1995; 92: 9230–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Greengard P, Valtorta F, Czernik AJ, Benfenati F. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 1993; 259: 780–5. [DOI] [PubMed] [Google Scholar]
  • 27. Haas CA, DeGennaro LJ. Multiple synapsin I messenger RNAs are differentially regulated during neuronal development. J Cell Biol 1988; 106: 95–203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Pieribone VA, Shuplikov O, Brodin L, Hilfiken‐Rothenflush S, Czernik A, Greengard P. Distinct pools of vesicles in neurotransmitter release. Nature 1995; 375: 493–7. [DOI] [PubMed] [Google Scholar]
  • 29. Südhof TC. The structure of the human synapsin I gene and protein. J Biol Chem. 1990; 265: 7849–52. [PubMed] [Google Scholar]
  • 30. Torri TF, Bossi M, Fesce R, Greengard P, Valtorta F. Synapsin I partially dissociates from synaptic vesicles during exocytosis induced by electrical stimulation. Neuron 1992; 9: 1143–53. [DOI] [PubMed] [Google Scholar]
  • 31. Nishimura E, Sasaki K, Maruyama K, Tsukada T, Yamaguchi K. Decrease in neuron‐restrictive silencer factor (NRSF) mRNA levels during differentiation of cultured neuroblastoma cells. Neurosci Lett 1996; 211: 101–4. [DOI] [PubMed] [Google Scholar]
  • 32. Palm K, Metsis M, Timmusk T. Neuron‐specific splicing of zinc finger transcription factor REST/NRSF/XBR is frequent in neuroblastomas and conserved in human, mouse and rat. Brain Res Mol Brain Res 1999; 72: 30–9. [DOI] [PubMed] [Google Scholar]
  • 33. Myers MW, Lazzarinr RA, Lee VM‐Y The human mid‐sized neurofilament subunits : a repeated protein sequence and the relationship of its gene to the intermediate filament gene family. EMBO J 1987; 6: 1617–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Helman LJ, Ahn TG, Levine MA, Allison A, Cohen PS, Cooper MJ, Cohn DV, Israel MA. Molecular cloning and primary structure of human chromogranin A (secretory protein I) cDNA. J Biol Chem. 1988; 263: 11559–63. [PubMed] [Google Scholar]
  • 35. Tokunaga K, Nakamura Y, Sakata K, Fujimori K, Ohkubo M, Sawada K, Sakiyama S. Enhanced expression of a glyceraldehyde‐3‐phosphate dehy‐drogenase gene in human lung cancers. Cancer Res 1987; 47: 5616–9. [PubMed] [Google Scholar]
  • 36. Kraner SD, Chong JA, Tsay H‐J, Mandel GX. Silencing the type II sodium channel gene: a model for neural‐specific gene regulation. Neuron 1993; 9: 37–44. [DOI] [PubMed] [Google Scholar]
  • 37. Lietz M, Cicchetti P, Thiel G. Inverse expression pattern of REST and synapsin I in human neuroblastoma cells. Biol Chem. 1998; 379: 1301–4. [PubMed] [Google Scholar]
  • 38. Madison DL, Krueger WH, Cheng D, Trapp BD, Pfeiffer SE. SNARE complex proteins, including the cognate pair VAMP‐2 and syntaxin‐4, are expressed in cultured oligodendrocytes. J Neurochem. 1999; 72: 988–98. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Science are provided here courtesy of Wiley

RESOURCES