Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors
Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors
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DOI：
10.1073/pnas.042372199
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发表时间：
2002-02-19
影响因子：
11.1
通讯作者：
Pantel, K
中科院分区：
文献类型：
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作者：
Solakoglu, O;Maierhofer, C;Pantel, K
骨髓是循环上皮肿瘤细胞的主要归巢点。本研究旨在评估可手术实体瘤患者骨髓中隐匿转移细胞的增殖能力，特别是其临床结果。我们从153例前列腺癌（n = 46）、乳腺癌（n = 45）、结肠癌（n = 33）和肾癌（n = 29）患者中抽取骨髓。大多数患者（87%）原发疾病无明显转移的临床体征[肿瘤-淋巴结-转移(TNM)-期UICC (Union international contrale le Cancer) I-III]。在特殊的细胞培养条件下，骨髓培养21 ~ 102 d后，124例（81%）患者通过细胞角蛋白染色检测到存活的上皮细胞。培养的上皮细胞携带Ki-ras2突变和数字染色体畸变。扩大肿瘤细胞的中位数最高的是前列腺癌（每烧瓶2,619个）。扩增肿瘤细胞数与患者的uicc分期（P = 0.03）或有无明显转移（P = 0.04）呈正相关。此外，肿瘤细胞的强烈扩张与癌症相关死亡率的增加（P = 0.007）和患者生存率的降低（P = 0.006）相关。总之，大多数癌症患者在原发肿瘤诊断时骨髓中都有活的肿瘤细胞，这些细胞的增殖潜力决定了临床结果。
Bone marrow is a major homing site for circulating epithelial tumor cells. The present study was aimed to assess the proliferative capacity of occult metastatic cells in bone marrow of patients with operable solid tumors especially with regard to their clinical outcome. We obtained bone marrow aspirates from 153 patients with carcinomas of the prostate (n = 46), breast (n = 45), colon (n = 33), and kidney (n = 29). Most of the patients (87%) had primary disease with no clinical signs of overt metastases [tumor-node-metastasis (TNM)-stage UICC (Union Internationale Contre le Cancer) I-III]. After bone marrow was cultured for 21-102 days under special cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 124 patients (81%). The cultured epithelial cells harbored Ki-ras2 mutations and numerical chromosomal aberrations. The highest median number of expanded tumor cells was observed in prostate cancer (2,619 per flask). There was a significant positive correlation between the number of expanded tumor cells and the UICC-stage of the patients (P = 0.03) or the presence of overt metastases (P = 0.04). Moreover, a strong expansion of tumor cells was correlated to an increased rate of cancer-related deaths (P = 0.007) and a reduced survival of the patients (P = 0.006). In conclusion, the majority of cancer patients have viable tumor cells in their bone marrow at primary tumor diagnosis, and the proliferative potential of these cells determines the clinical outcome.