Kloen P, Jennings C L, Gebhardt M C, Springfield D S, Mankin H J
Department of Orthopedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Int J Cancer. 1994 Aug 1;58(3):440-5. doi: 10.1002/ijc.2910580323.
Transforming growth factor-beta (TGF-beta) is a polypeptide with multiple physiological functions. Isoforms of this growth factor have important roles in control of the cell cycle, in regulation of cell-cell interactions and in growth and development. Malignant transformation has been shown to be associated with increased expression of TGF-beta. Since bone is the largest storage site and producer of TGF-beta, we speculated on the existence of an autocrine mechanism in osteosarcoma, a malignant bone tumor. Expression of TGF-beta cell surface receptors, effects on growth of TGF-beta and TGF-beta antibodies and production of 2 TGF-beta isoforms were studied in a panel of 7 osteosarcoma cell lines. In contrast to most previous reports on the effects of TGF-beta on osteosarcoma cell growth, we found a mitogenic effect of TGF-beta 1 in 4 of 7 osteosarcoma cell lines. Receptor profiles for TGF-beta were aberrant in 5 of the 7 cell lines tested, and production of TGF-beta 1 and TGF-beta 2 varied among cell lines. Addition of anti-TGF-beta antagonized the effects of endogenous TGF-beta. Our results suggest a potential role of TGF-beta in autocrine growth control of osteosarcoma cells.
转化生长因子-β(TGF-β)是一种具有多种生理功能的多肽。该生长因子的亚型在细胞周期调控、细胞间相互作用调节以及生长发育过程中发挥着重要作用。恶性转化已被证明与TGF-β表达增加有关。由于骨骼是TGF-β最大的储存部位和产生部位,我们推测骨肉瘤(一种恶性骨肿瘤)中存在自分泌机制。我们在一组7种骨肉瘤细胞系中研究了TGF-β细胞表面受体的表达、TGF-β对细胞生长的影响、TGF-β抗体以及两种TGF-β亚型的产生情况。与之前大多数关于TGF-β对骨肉瘤细胞生长影响的报道不同,我们发现7种骨肉瘤细胞系中有4种对TGF-β1有促有丝分裂作用。在所测试的7种细胞系中,有5种的TGF-β受体谱异常,且各细胞系中TGF-β1和TGF-β2的产生情况各不相同。添加抗TGF-β可拮抗内源性TGF-β的作用。我们的结果表明TGF-β在骨肉瘤细胞的自分泌生长控制中可能发挥作用。