A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro
A bone-seeking clone exhibits different biological properties from the MDA-MB-231 parental human breast cancer cells and a brain-seeking clone in vivo and in vitro
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DOI：
10.1359/jbmr.2001.16.8.1486
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发表时间：
2001-08-01
影响因子：
6.2
通讯作者：
Nishimura, R
中科院分区：
文献类型：
--
作者：
Yoneda, T;Williams, PJ;Nishimura, R
乳腺癌有扩散到骨骼的倾向。乳腺癌优先转移到骨的机制尚不清楚。我们假设，乳腺癌细胞发展骨转移有能力促进其在骨中的定植。为了验证这一假设，我们建立了骨寻求（MDA-231 BO）和脑寻求（MDA-231 BR）克隆的人乳腺癌细胞系MDA-MB-231通过重复连续传代在裸鼠和体外的转移细胞从骨和脑转移，分别。这些克隆进行了检查，区分生物学特性，并与MDA-231亲本细胞（MDA-231 P）在体内和体外进行了比较。MDA-231 BR和MDA-231 BO在原位位点显示出与MDA-231 P相同的致瘤性。MDA-231 P接种到心脏中，在骨、脑、卵巢和肾上腺中发生转移。另一方面，MDA-231 BO仅转移到骨，溶骨性病变比MDA-231 P更大。MDA-231 BR仅扩散至脑，未发生骨转移。在培养中，在不存在或存在转化生长因子β（TGF-β）的情况下，MDA-231 BO产生的甲状旁腺相关蛋白（PTH-rP）比MDA-231 BR和MDA-231 P更大量。此外，MDA-231 BO在软琼脂中的锚定非依赖性生长不受TGF-β抑制，而TGF-β显著抑制MDA-231 P和MDA-231 BR的生长。胰岛素样生长因子I（IGF-I）显著促进MDA-231 BO的锚定非依赖性生长，而MDA-231 BR或MDA-231 P分别观察到边缘或无刺激。我们的数据表明，这些表型变化允许乳腺癌细胞促进骨吸收，存活，并在骨中增殖，从而导致骨转移的建立。
Breast cancer has a predilection for spreading to bone. The mechanism of preferential metastasis of breast cancer to bone is unknown. We hypothesize that breast cancer cells that develop bone metastases have the capacity to facilitate their colonization in bone. To examine this hypothesis, we established bone-seeking (MDA-231BO) and brain-seeking (MDA-231BR) clones of the human breast cancer cell line MDA-MB-231 by repeated sequential passages in nude mice and in vitro of metastatic cells obtained from bone and brain metastases, respectively. These clones were examined for distinguishing biological characteristics and compared with the MDA-231 parental cells (MDA-231P) in vivo and in vitro. Both the MDA-231BR and the MDA-231BO showed identical tumorigenicity to MDA-231P at the orthotopic site. MDA-231P that was inoculated into the heart developed metastases in bone, brain, ovary, and adrenal glands. On the other hand, MDA-231BO exclusively metastasized to bone with larger osteolytic lesions than MDA-231P. MDA-231BR exclusively disseminated to brain and failed to develop bone metastases. In culture, MDA-231BO produced greater amounts of parathyroid hormone-related protein (PTH-rP) than MDA-231BR and MDA-231P in the absence or presence of transforming growth factor beta (TGF-beta). Furthermore, the anchorage-independent growth of MDA-231BO in soft agar was not inhibited by TGF-beta, whereas TGF-beta profoundly inhibited the growth of MDA-231P and MDA-231BR. Insulin-like growth factor I (IGF-I) markedly promoted the anchorage-independent growth of MDA-231BO, whereas marginal or no stimulation was observed in MDA-231BR or MDA-231P, respectively. Our data suggest that these phenotypic changes allow breast cancer cells to promote osteoclastic bone resorption, survive, and proliferate in bone, which consequently leads to the establishment of bone metastases.