A mouse tumor-derived osteolytic factor stimulates bone resorption by a mechanism involving local prostaglandins production in bone.
A mouse tumor-derived osteolytic factor stimulates bone resorption by a mechanism involving local prostaglandins production in bone.
复制标题
小鼠肿瘤来源的溶骨因子通过涉及骨中局部前列腺素产生的机制刺激骨吸收。
DOI：
10.1016/0304-4165(85)90162-x
复制
发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Baylink,DJ
中科院分区：
文献类型：
--
作者：
Lau,KH;Lee,MY;Linkhart,TA;Mohan,S;Vermeiden,J;Liu,CC;Baylink,DJ
以CE小鼠乳腺肿瘤组织为条件的体外培养液具有剂量依赖性溶骨活性。溶骨活性不溶于二氯甲烷和乙酸乙酯，表明其不归因于维生素D代谢产物或野牡丹素。然而，乳腺肿瘤条件培养液在体外刺激小鼠颅骨前列腺素E2的产生和释放，并且乳腺肿瘤条件培养液在体外对骨吸收的刺激被一定剂量的吲哚美辛阻断，该剂量的吲哚美辛阻止了小鼠颅骨前列腺素E2的产生和释放。甲状旁腺激素（PTH）的吸收活性不受相同剂量吲哚美辛的影响，表明溶骨因子不是PTH。这进一步得到了观察结果的支持，即小鼠肾细胞cAMP的产生受到PTH的刺激，而不仅仅是受到乙酸乙酯提取的乳腺肿瘤条件培养基的水相的刺激。除了溶骨活性，乳腺肿瘤条件培养基含有剂量依赖性的骨细胞促有丝分裂活性，通过刺激[3H]胸苷掺入三氯乙酸不溶性大分子和骨细胞单层培养物中骨细胞数量的相应增加来证明。乳腺肿瘤条件培养基还含有剂量依赖性转化生长因子（TGF）样活性，如其将非转化细胞的锚定依赖性生长转化为锚定非依赖性生长的能力所定义。乳腺肿瘤条件培养液中的TGF不与表皮生长因子（EGF）竞争EGF受体结合，但EGF能显著增强其转化活性，表明其为β型TGF。溶骨和促有丝分裂活性均不可透析，对还原剂敏感，且不可通过二氯甲烷和乙酸乙酯提取去除。此外，TGF活性没有被乙酸乙酯提取去除。因此，这些活动在乳腺肿瘤条件培养基可能是由相同的分子介导的可能性必须考虑。总之，我们的数据表明，CE小鼠乳腺癌细胞产生并分泌到培养基中的溶骨因子，既不是PTH也不是前列腺素，它刺激骨中前列腺素E2的局部合成，这反过来又增加了体外骨吸收。
Culture medium which was conditioned by tissue of a CE mouse breast tumor in vitro containes dose-dependent osteolytic activity. The osteolytic activity was not soluble in dichloromethane and ethylacetate, indicating that it was not attributable to vitamine D metabolites or prostaglandins. HOwever, breast tumor-conditioned medium stimulated production and release of prostaglandin E2from mouse calvaria in vitro, and the stimulation of bone resorption in vitro by breast tumor-conditioned medium was blocked by a dose of indomethacin that prevented stimulation of mouse calvarial prostaglandin E2production and release. The resorptive activity of parathyroid hormone(PTH) was not affected by the same dose of indomethacin, suggesting that the osteolytic factor was not PTH. This was further supported by observation that mouse kidney cell cAMP production was stimulated by PTH, but not only by the aqueous phase of ethylacetate-extracted breast tumor-conditioned medium. In addition to osteolytic activity, breast tumor-conditioned medium contained a dose-dependent bone cell mitogenic activity, demonstrated by the stimulation of [3H]thymidine incorporation into trichloroacetic acid-insoluble macromolecules and a corresponding increase in bone cell number in monolayer cultures of bone cells. Breast tumor-conditioned medium also contained a dose-dependent transforming growth factor-(TGF)-like activity as defined by its ability to transform anchorage-dependent growth of nontransformed cells to anchorage-independent growth. The TGF in breast tumor-conditioned medium did not compete with epidermal growth factor (EGF) for EGF receptor binding, but its transforming activity was greatly enhanced by EGF, indicating that it was a β-type TGF. Both the osteolytic and mitogenic activities were nondialyzable, sensitive to reducing agent, and not removable by dichloromethane and ethylacetate extractions. Furthermore, the TGF activity was not removed by the ethylacetate extraction. Thus, the possibility that these activities in breast tumor-conditioned medium might be mediated by the same molecule must be considered. In summary, our data suggest that the CE mouse mammary carcinoma cells produce and secret into the culture medium an osteolytic factor which is neither PTH nor prostaglandin and which stimulates local synthesis in bone of prostaglandin E2which in turn increased bone resorption in vitro.