Expression of the neural cell adhesion molecule and polysialic acid in human neuroblastoma cell lines.
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Expression of the neural cell adhesion molecule and polysialic acid in human neuroblastoma cell lines. / Valentiner, Ursula; Mühlenhoff, Martina; Lehmann, Ulrich; Hildebrandt, Herbert; Schumacher, Udo.
in: INT J ONCOL, Jahrgang 39, Nr. 2, 2, 2011, S. 417-424.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Expression of the neural cell adhesion molecule and polysialic acid in human neuroblastoma cell lines.
AU - Valentiner, Ursula
AU - Mühlenhoff, Martina
AU - Lehmann, Ulrich
AU - Hildebrandt, Herbert
AU - Schumacher, Udo
PY - 2011
Y1 - 2011
N2 - The neural cell adhesion molecule NCAM is a cell surface glycoprotein of the immunoglobulin superfamily and is widely expressed in tumours of neuroectodermal origin such as neuroblastoma. NCAM can be decorated by the carbohydrate polymer polysialic acid (polySia), which attenuates NCAM-mediated cell adhesion and increases cellular motility. The key enzymes in the biosynthesis of polySia are the two polysialyltransferases ST8SiaII and ST8SiaIV. In the present study, expression of NCAM, polySia-NCAM, ST8SiaII and ST8SiaIV was investigated in five human neuroblastoma cell lines before and after xenografting into SCID mice by immunohistochemistry, Western blot analysis and real-time PCR. Results were correlated with the metastatic potential. In vitro, three cell lines (LAN-1, LAN-5 and SH-SY5Y) were positive for polySia attached to the transmembrane isoforms NCAM-140 and NCAM-180, whereas Kelly and SK-N-SH cells were negative for NCAM and polySia. In the presence of NCAM, the level of polySia correlated with the amount of polysialyltransferase transcripts, which were highest in LAN-1, LAN?5 and SH-SY5Y cells. In the respective primary tumours grown in SCID mice, the expression patterns of NCAM, polySia and polysialyl-transferases were similar to those observed in vitro. After subcutaneous engraftment, polySia-NCAM-positive neuroblastoma developed disseminated micrometastases, a metastatic pattern that was not observed for tumours derived from NCAM-negative cell lines. Together, this indicates that the presence of polySia reduces the adhesiveness of tumour cells and promotes dissemination.
AB - The neural cell adhesion molecule NCAM is a cell surface glycoprotein of the immunoglobulin superfamily and is widely expressed in tumours of neuroectodermal origin such as neuroblastoma. NCAM can be decorated by the carbohydrate polymer polysialic acid (polySia), which attenuates NCAM-mediated cell adhesion and increases cellular motility. The key enzymes in the biosynthesis of polySia are the two polysialyltransferases ST8SiaII and ST8SiaIV. In the present study, expression of NCAM, polySia-NCAM, ST8SiaII and ST8SiaIV was investigated in five human neuroblastoma cell lines before and after xenografting into SCID mice by immunohistochemistry, Western blot analysis and real-time PCR. Results were correlated with the metastatic potential. In vitro, three cell lines (LAN-1, LAN-5 and SH-SY5Y) were positive for polySia attached to the transmembrane isoforms NCAM-140 and NCAM-180, whereas Kelly and SK-N-SH cells were negative for NCAM and polySia. In the presence of NCAM, the level of polySia correlated with the amount of polysialyltransferase transcripts, which were highest in LAN-1, LAN?5 and SH-SY5Y cells. In the respective primary tumours grown in SCID mice, the expression patterns of NCAM, polySia and polysialyl-transferases were similar to those observed in vitro. After subcutaneous engraftment, polySia-NCAM-positive neuroblastoma developed disseminated micrometastases, a metastatic pattern that was not observed for tumours derived from NCAM-negative cell lines. Together, this indicates that the presence of polySia reduces the adhesiveness of tumour cells and promotes dissemination.
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred BALB C
KW - Cell Line, Tumor
KW - Transcription, Genetic
KW - Gene Expression Regulation, Neoplastic
KW - Mice, SCID
KW - Lung Neoplasms/physiopathology/secondary
KW - Neural Cell Adhesion Molecules/genetics/metabolism
KW - Neuroblastoma/physiopathology
KW - Sialic Acids/metabolism
KW - Sialyltransferases/genetics/metabolism
KW - Xenograft Model Antitumor Assays
KW - Animals
KW - Humans
KW - Mice
KW - Mice, Inbred BALB C
KW - Cell Line, Tumor
KW - Transcription, Genetic
KW - Gene Expression Regulation, Neoplastic
KW - Mice, SCID
KW - Lung Neoplasms/physiopathology/secondary
KW - Neural Cell Adhesion Molecules/genetics/metabolism
KW - Neuroblastoma/physiopathology
KW - Sialic Acids/metabolism
KW - Sialyltransferases/genetics/metabolism
KW - Xenograft Model Antitumor Assays
M3 - SCORING: Journal article
VL - 39
SP - 417
EP - 424
JO - INT J ONCOL
JF - INT J ONCOL
SN - 1019-6439
IS - 2
M1 - 2
ER -
