Brooks B, Bundred N J, Howell A, Lang S H, Testa N G
CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.
Int J Cancer. 1997 Nov 27;73(5):690-6. doi: 10.1002/(sici)1097-0215(19971127)73:5<690::aid-ijc13>3.0.co;2-a.
A model has been established using primary human cell culture to study the cell biology of breast cancer metastasis to bone marrow. Mammary epithelia were obtained in single cell suspension from tumour (macroscopically involved), benign (macroscopically uninvolved) and normal (reduction mammoplasty) breast tissue as well as from locally involved lymph nodes. Stromal layers were generated from long-term cultures of human bone marrow or from mammary fibroblasts derived from normal or malignant tissue. The interaction between epithelia and stroma has been studied in terms of adhesion of the epithelia to the stroma and their subsequent growth in co-culture. Our results show that when assayed up to 9 hr after plating, epithelial cells from malignant tissue (14 primary tumours and 9 metastases in lymph nodes) displayed a significant preference for adhesion to bone marrow stroma compared with mammary fibroblasts. In contrast, epithelial cells from 4 normal and 2 of 4 benign samples showed no significant preferential adherence. Subsequent co-culture of mammary epithelia with each of the 3 stromal layers revealed that under serum-free, in vitro conditions, bone marrow stromal layers did not provide an advantageous environment for colony growth, in contrast to their ability to provide a preferential substratum for adhesion.
已建立一种利用原代人细胞培养来研究乳腺癌向骨髓转移的细胞生物学的模型。从肿瘤（肉眼可见受累）、良性（肉眼可见未受累）和正常（缩乳术）乳腺组织以及局部受累的淋巴结中获取单细胞悬液形式的乳腺上皮细胞。基质层由人骨髓的长期培养物或源自正常或恶性组织的乳腺成纤维细胞产生。上皮细胞与基质之间的相互作用已根据上皮细胞与基质的黏附及其在共培养中的后续生长情况进行了研究。我们的结果表明，在接种后长达9小时进行检测时，与乳腺成纤维细胞相比，来自恶性组织（14个原发性肿瘤和9个淋巴结转移灶）的上皮细胞对黏附于骨髓基质表现出显著偏好。相比之下，来自4个正常样本和4个良性样本中的2个的上皮细胞未表现出显著的优先黏附。随后将乳腺上皮细胞与3种基质层中的每一种进行共培养，结果显示，在无血清的体外条件下，与它们为黏附提供优先底物的能力形成对比的是，骨髓基质层并未为集落生长提供有利环境。
