COINCIDENTAL ACQUISITION OF GROWTH AUTONOMY AND METASTATIC POTENTIAL DURING THE MALIGNANT TRANSFORMATION OF FACTOR-DEPENDENT CCL39 LUNG FIBROBLASTS
COINCIDENTAL ACQUISITION OF GROWTH AUTONOMY AND METASTATIC POTENTIAL DURING THE MALIGNANT TRANSFORMATION OF FACTOR-DEPENDENT CCL39 LUNG FIBROBLASTS
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DOI：
10.1093/jnci/80.5.318
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发表时间：
1988-05-04
影响因子：
10.3
通讯作者：
LAGARDE, AE
中科院分区：
文献类型：
--
作者：
CHADWICK, DE;LAGARDE, AE
皮下植入BALB/c裸鼠后，因子依赖性和癌前病变中国仓鼠肺成纤维细胞（CCL 39）发展成肿瘤，偶尔扩散和产生肺转移。与需要几种生长因子（胰岛素、α-胰岛素）的CCL 39细胞不同，凝血酶，表皮生长因子）在培养物中增殖，转移性肿瘤细胞在无血清培养基中自主分裂。独立分离的原发性肿瘤的再植入显示，它们包括以可变频率存在的因子非依赖性克隆，以及在sc或iv接种后扩散到肺的恶性克隆。由此产生的转移瘤总是包含能够在无血清培养基中分裂的细胞，并且可能代表了原发性肿瘤中自主变异的后代。在体外选择的用于降低生长因子需求的10种CCL 39变体中，两种在sc和iv接种后具有转移性。这些细胞系是唯一在没有生长因子的情况下快速复制的细胞系。与myc转染子不同，用激活的Harvey ras癌基因转化或用多瘤病毒感染的CCL 39成纤维细胞是转移性的和自主的。总之，这些观察结果与CCL 39肿瘤细胞的转移潜力与其满足生长因子需求的能力一致，从而以自主方式分裂。
After sc implantation into BALB/c nude mice, factor-dependent and premalignant Chinese hamster lung fibroblasts (CCL39) developed into tumors that occasionally disseminated and produced pulmonary metastases. Unlike CCL39 cells that required several growth factors (insulin, .alpha.-thrombin, epidermal growth factor) to proliferate in culture, metastatic tumor cells divided autonomously in serum-free medium. The re-implantation of independently isolated primary tumors revealed that they comprised factor-independent clones present at a variable frequency, as well as malignant clones that disseminated to the lungs after sc or iv inoculation. The resulting metastases invariably contained cells that were able to divide in serum-free medium and that presumably represented the progeny of autonomous variants populating the primary tumors. Among ten CCL39 variants selected in vitro for reduced growth factor requirements, two were metastatic upon sc and iv inoculation. These cell lines were the only ones that replicated rapidly in the absence of growth factors. Unlike myc transfectants, CCL39 fibroblasts that were transformed with an activated Harvey ras oncogene or that were infected with polyomavirus were both metastatic and autonomous. Taken together, these observations are consistent with the notion that the metastatic potential of CCL39 tumor cells coincides with their ability to obviate growth factor requirements and thus to divide in an autonomous fashion.