Timeus F, Crescenzio N, Valle P, Pistamiglio P, Piglione M, Garelli E, Ricotti E, Rocchi P, Strippoli P, Cordero di Montezemolo L, Madon E, Ramenghi U, Basso G
Dipartimento di Scienze Pediatriche, University of Torino, Italy.
Exp Hematol. 1997 Nov;25(12):1253-60.
Stem cell factor (SCF) is a glycoprotein growth factor produced by marrow stromal cells that acts after binding to its specific surface receptor, which is the protein encoded by the protooncogene c-kit. SCF synergizes with specific lineage factors in promoting the proliferation of primitive hematopoietic progenitors, and has been administered to expand the pool of these progenitors in cancer patients treated with high-dose chemotherapy. SCF and its c-kit receptor are expressed by some tumor cells, including myeloid leukemia, breast carcinoma, small cell lung carcinoma, melanoma, gynecological tumors, and testicular germ cell tumors. Previous studies of SCF in neuroblastoma have produced conflicting conclusions. To explore the role of SCF in neuroblastoma, we studied five neuroblastoma lines (IMR-5, SK-N-SH, SK-N-BE, AF8, and SJ-N-KP) and the neuroepithelioma line CHP-100. All lines expressed mRNA for c-kit and c-kit protein at low intensity as measured by flow cytometry, and secreted SCF in medium culture as shown by ELISA. Exogenous SCF did not modify 3H thymidine uptake in the neuroblastoma and neuroepithelioma cell lines. After 6 days' culture in the presence of anti-c-kit, the number of viable neuroblastoma cells was significantly lower than the control, and terminal deoxynucleotidyl transferase assay showed a substantial increase of apoptotic cells: The percentage of positive cells was 1-3% in the control lines, whereas in the presence of anti c-kit it varied from 29% of SK-N-BE to 92% of CHP-100. After 9 days' culture in the presence of anti-c-kit, no viable cells were detectable. These data indicate that SCF is produced by some neuroblastoma cell lines via an autocrine loop to protect them from apoptosis.
干细胞因子（SCF）是一种由骨髓基质细胞产生的糖蛋白生长因子，它在与其特定表面受体结合后发挥作用，该受体是原癌基因c-kit编码的蛋白质。SCF在促进原始造血祖细胞增殖方面与特定谱系因子协同作用，并已用于扩大接受大剂量化疗的癌症患者中这些祖细胞的数量。SCF及其c-kit受体在一些肿瘤细胞中表达，包括髓系白血病、乳腺癌、小细胞肺癌、黑色素瘤、妇科肿瘤和睾丸生殖细胞肿瘤。先前关于SCF在神经母细胞瘤中的研究得出了相互矛盾的结论。为了探究SCF在神经母细胞瘤中的作用，我们研究了5种神经母细胞瘤细胞系（IMR-5、SK-N-SH、SK-N-BE、AF8和SJ-N-KP）以及神经上皮瘤细胞系CHP-100。通过流式细胞术检测，所有细胞系均低强度表达c-kit的mRNA和c-kit蛋白，并且ELISA检测显示在培养基培养中分泌SCF。外源性SCF并未改变神经母细胞瘤和神经上皮瘤细胞系中3H胸苷的摄取。在抗c-kit存在下培养6天后，存活的神经母细胞瘤细胞数量明显低于对照组，末端脱氧核苷酸转移酶检测显示凋亡细胞大幅增加：对照组细胞系中阳性细胞的百分比为1%-3%，而在抗c-kit存在的情况下，其范围从SK-N-BE的29%到CHP-100的92%不等。在抗c-kit存在下培养9天后，未检测到存活细胞。这些数据表明，一些神经母细胞瘤细胞系通过自分泌环路产生SCF以保护它们免于凋亡。
