Overexpressions of nerve growth factor and its tropomyosin-related kinase A receptor on chordoma cells.
METHODS
Immunohistochemistry and in situ apoptosis detection assay were performed on chordoma and notochordal cells.


OBJECTIVE
To investigate the expression levels of nerve growth factor (NGF) and its 2 receptors, tropomyosin-related kinase A (TrkA) and p75, as well as proliferation potential and apoptosis indexes in chordoma and notochordal cells.


BACKGROUND
Chordomas arise from primitive notochordal remnants. Why these notochordal remnants undergo malignant transformation to chordoma remains unknown. The binding of NGF to the TrkA receptor promotes cell survival, while its binding to the p75 receptor triggers apoptosis. If there is simultaneous expression of both receptors, the effect of TrkA supersedes and the cells survive.


METHODS
We examined 10 surgically obtained sacral chordoma tissue samples to determine the expressions of NGF and TrkA and p75 receptors as well as markers of cellular proliferation and apoptosis. As controls, we used notochordal cells of L4-L5 discs obtained from ten 1-month old rats. We quantified the expressions of NGF and TrkA and p75 receptors as well as markers of cellular proliferation and apoptosis for both groups, respectively.


RESULTS
Chordoma and notochordal cells both expressed NGF as well as TrkA and p75 receptors. While the mean percentage of p75 receptor expression was very similar between chordoma and notochordal cells (P = 0.394), the mean percentages of TrkA and NGF expressions were significantly higher in chordoma cells than in notochordal cells (both P = 0.002). The mean proliferation potential index of chordoma cells was significantly higher than in notochordal cells (P < 0.01). Conversely, the mean apoptosis index of chordoma cells was significantly lower compared with that of notochordal cells (P = 0.03).


CONCLUSIONS
The current results suggest that increased expressions of NGF and TrkA receptor in chordoma cells might be a possible mechanism of malignant transformation of notochordal remnants to chordoma by negating apoptotic signal of p75 receptor.
Park
Jong-Beom
JB
Department of Orthopaedic Surgery, Catholic University of Korea School of Medicine, Seoul, Korea. spinepjb@catholic.ac.kr
Lee
Choon-Ki
CK
Koh
Jae-Soo
JS
Lee
Jin-Kyung
JK
Park
Eun-Young
EY
Riew
K Daniel
KD
D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002817:Chordoma / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D009672:Notochord / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D020932:Nerve Growth Factor; D020917:Receptor, trkA