Control of proliferation and survival of C6 glioma cells with modification of the nerve growth factor autocrine system

被引:15
作者
Watanabe, T [1 ]
Katayama, Y [1 ]
Kimura, S [1 ]
Yoshino, A [1 ]
机构
[1] Nihon Univ, Sch Med, Dept Neurol Surg, Itabashi Ku, Tokyo 173, Japan
关键词
apoptosis; cell death; C6; glioma; nerve growth factor;
D O I
10.1023/A:1006127624487
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Nerve growth factor (NGF) plays an important physiological role in differentiation and survival of various types of neurons. Glial cells and glial tumor cells synthesize multiple neurotrophic factors including NGF and secrete them into the surrounding environment; however, the mechanisms of NGF and the significance of NGF receptors have not been studied in detail. The C6 glioma cell line can synthesize NGF, respond to exogenous application of NGF and stimulate the expression of NGF receptor in an autocrine manner. In order to determine the significance of such an NGF autocrine system, the effects of exposure to exogenous NGF and deprivation of endogenous NGF were examined in a C6 glioma cell line in vitro. Exogenous NGF significantly inhibited maintenance of the cell number and thymidine incorporation. Morphological changes, including the formation of growth cones, outgrowth of processes and cellular hypertrophy, were observed, concurrently, indicating that exogenous NGF stimulated differentiation and thereby inhibited proliferation of the cells. Deprivation of endogenous NGF with anti-NGF antibody elicited a rapid decrease in cell number and thymidine incorporation, and led almost all of the cells to death within 8 days. The protein synthesis inhibitor, cycloheximide, strongly inhibited the death of NGF-deprived cells, suggesting the involvement of an active process requiring synthesis of suicide proteins. These findings imply that the NGF autocrine system plays a significant role in regulating the differentiation and survival of C6 glioma cells, similarly to neuronal cells.
引用
收藏
页码:121 / 128
页数:8
相关论文
共 29 条
[2]   EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION DURING MORPHOLOGICAL-DIFFERENTIATION OF PHEOCHROMOCYTOMA CELLS, INDUCED BY NERVE GROWTH-FACTOR OR DIBUTYRYL-CYCLIC-AMP [J].
BOONSTRA, J ;
MUMMERY, CL ;
FEYEN, A ;
DEHOOG, WJ ;
VANDERSAAG, PT ;
DELAAT, SW .
JOURNAL OF CELLULAR PHYSIOLOGY, 1987, 131 (03) :409-417
[3]   NERVE GROWTH-FACTOR - BIOCHEMISTRY, SYNTHESIS, AND MECHANISM OF ACTION [J].
GREENE, LA ;
SHOOTER, EM .
ANNUAL REVIEW OF NEUROSCIENCE, 1980, 3 :353-402
[4]   ESTABLISHMENT OF A NORADRENERGIC CLONAL LINE OF RAT ADRENAL PHEOCHROMOCYTOMA CELLS WHICH RESPOND TO NERVE GROWTH-FACTOR [J].
GREENE, LA ;
TISCHLER, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1976, 73 (07) :2424-2428
[5]   ONTOGENY OF THE NERVE GROWTH-FACTOR RECEPTOR IN PRIMARY CULTURES OF NEURAL CREST CELLS [J].
GREINER, CAM ;
LLOYD, AT ;
GUROFF, G .
DEVELOPMENTAL BRAIN RESEARCH, 1986, 26 (01) :145-150
[6]   USE OF AVIDIN-BIOTIN-PEROXIDASE COMPLEX (ABC) IN IMMUNOPEROXIDASE TECHNIQUES - A COMPARISON BETWEEN ABC AND UNLABELED ANTIBODY (PAP) PROCEDURES [J].
HSU, SM ;
RAINE, L ;
FANGER, H .
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 1981, 29 (04) :577-580
[7]  
JENSEN LM, 1992, J BIOL CHEM, V267, P19325
[8]   DORSAL-ROOT GANGLION NEURONS ARE DESTROYED BY EXPOSURE IN UTERO TO MATERNAL ANTIBODY TO NERVE GROWTH-FACTOR [J].
JOHNSON, EM ;
GORIN, PD ;
BRANDEIS, LD ;
PEARSON, J .
SCIENCE, 1980, 210 (4472) :916-918
[9]   TYROSINE PHOSPHORYLATION AND TYROSINE KINASE-ACTIVITY OF THE TRK PROTOONCOGENE PRODUCT INDUCED BY NGF [J].
KAPLAN, DR ;
MARTINZANCA, D ;
PARADA, LF .
NATURE, 1991, 350 (6314) :158-160
[10]   THE TRK PROTOONCOGENE PRODUCT - A SIGNAL TRANSDUCING RECEPTOR FOR NERVE GROWTH-FACTOR [J].
KAPLAN, DR ;
HEMPSTEAD, BL ;
MARTINZANCA, D ;
CHAO, MV ;
PARADA, LF .
SCIENCE, 1991, 252 (5005) :554-558