Pierschbacher M D, Dedhar S, Ruoslahti E, Argraves S, Suzuki S
Cancer Research Center, La Jolla Cancer Research Foundation, California 92037.
Ciba Found Symp. 1988;136:131-41. doi: 10.1002/9780470513637.ch9.
MG-63 human osteosarcoma cells were selected for attachment and growth in increasing concentrations of a synthetic peptide containing the cell attachment-promoting Arg-Gly-Asp (RGD) sequence derived from the cell-binding region of fibronectin. Cells capable of attachment and growth in 5 mM concentrations of a peptide having the sequence Gly-Arg-Gly-Asp-Ser-Pro overproduce the cell surface receptor for fibronectin. No increase in fibronectin receptor gene copy number was detected by Southern blot analysis. The peptide-resistant MG-63.3A cells look very different from the MG-63 cells and resemble osteocytes. The resistant cells also grow more slowly than MG-63 cells. The enhanced expression of the fibronectin receptor on the resistant cells indicates that cells can regulate the amount of this receptor on their surface in response to environmental factors and that this may affect the phenotypic properties of the cell. MG-63.3A cells differ from MG-63 cells in their ability to form a calcified matrix in vitro and in their increased synthesis of type I collagen. The MG-63.3A cells synthesize 50-100-fold less prostaglandin E2, a mediator of bone resorption, than MG-63 cells. There is an overall down-regulation of chondroitin sulphate proteoglycans in MG-63.3A cells. These results are consistent with the hypothesis that such proteoglycans interfere with calcium phosphate deposition and with the observation that chondroitin sulphate is increased in a wide variety of neoplasms but is absent or in small amounts in normal tissue. We conclude that MG-63.3A cells represent a more differentiated cell type with osteoblast-like properties.
选择MG-63人骨肉瘤细胞,使其在含有源自纤连蛋白细胞结合区域、具有促进细胞黏附作用的精氨酸-甘氨酸-天冬氨酸(RGD)序列的合成肽浓度不断增加的环境中黏附并生长。能够在5 mM浓度的具有甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸-脯氨酸序列的肽中黏附并生长的细胞,其纤连蛋白细胞表面受体产生过量。通过Southern印迹分析未检测到纤连蛋白受体基因拷贝数增加。抗肽的MG-63.3A细胞与MG-63细胞外观差异很大,类似骨细胞。抗性细胞的生长也比MG-63细胞慢。抗性细胞上纤连蛋白受体的表达增强,表明细胞可根据环境因素调节其表面该受体的数量,这可能会影响细胞的表型特性。MG-63.3A细胞与MG-63细胞在体外形成钙化基质的能力以及I型胶原蛋白合成增加方面存在差异。MG-63.3A细胞合成的前列腺素E2(一种骨吸收介质)比MG-63细胞少50至100倍。MG-63.3A细胞中硫酸软骨素蛋白聚糖总体下调。这些结果与以下假设一致,即此类蛋白聚糖会干扰磷酸钙沉积,也与以下观察结果一致,即在多种肿瘤中硫酸软骨素增加,但在正常组织中不存在或含量很少。我们得出结论,MG-63.3A细胞代表一种具有成骨细胞样特性的更分化的细胞类型。