CHARACTERIZATION OF A HIGHLY INVASIVE AND SPONTANEOUSLY METASTATIC HUMAN-MALIGNANT MELANOMA CELL-LINE
CHARACTERIZATION OF A HIGHLY INVASIVE AND SPONTANEOUSLY METASTATIC HUMAN-MALIGNANT MELANOMA CELL-LINE
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DOI：
10.1002/ijc.2910470211
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发表时间：
1991-01-21
影响因子：
6.4
通讯作者：
HENDRIX, MJC
中科院分区：
文献类型：
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作者：
WELCH, DR;BISI, JE;HENDRIX, MJC
虽然恶性黑色素瘤的发病率和死亡率正在迅速上升，但很少有实验模型模拟与人类疾病发病机制相关的高转移性，使得对该疾病的研究变得困难。因此，需要新的人类模型来了解黑色素瘤生物学，特别是其转移特性。在这里，我们描述了C8161，一种高度侵袭性和自发转移性的人黑色素瘤细胞系，它在无胸腺裸鼠皮下组织中逐渐生长，平均倍增时间约为6天。当肿瘤直径达到1 cm时，淋巴结、皮肤、腹膜壁、脾和肺中的无色素转移已经形成。通过将C8161与来自具有不同转移倾向的其他充分表征的人恶性黑色素瘤（A375和MeWo）的变体进行比较，检查了C8161。与其他黑色素瘤细胞系相比，C8161在MICS中侵袭重建基底膜屏障的能力高2- 14倍，IV型胶原酶mRNA水平和胶原溶解活性相应较高。同样，观察到与固定化RBM或HUVEC单层的差异粘附，但与恶性性质的等级顺序无关。最近，ICAM-1的表面表达和人类黑色素瘤继发性肿瘤形成之间的相关性已在几个实验室中被描述。比较了C8161、A375和MeWo人黑色素瘤中ICAM-1的基础水平，但未发现与转移潜能相关。使用北方印迹分析比较C8161细胞中的原癌基因表达与A375 P和A375 M变体。c-myc的表达是A375变体的6倍; c-fos的表达是A375 P的3.4倍，是A375 M的1.7倍; c-jun在C8161细胞中的表达分别是A375 P和A375 M的2.5倍和2.1倍。由于C8161是如此高度恶性，易于实验操作，并且其在裸鼠中的行为模拟恶性黑色素瘤的临床过程，因此该细胞系将被证明对于研究与人类黑色素瘤肿瘤进展相关的性质是有价值的。
Although the incidence of, and deaths due to, malignant melanoma are rising at a rapid rate, few experimental models mimic the highly metastatic properties associated with the pathogenesis of the human disease, making study of the disease difficult. Thus, new human models are required to understand melanoma biology, especially its metastatic properties. Here we describe C8161, a highly invasive and spontaneously metastatic human melanoma cell line, which grows progressively in the subcutis of athymic nude mice with an average doubling time of approximately 6 days. By the time the tumor reaches a diameter of 1 cm, amelanotic metastases in lymph nodes, skin, peritoneal wall, spleen and lungs have formed. By comparing C8161 to variants from other well-characterized human malignant melanomas (A375 and MeWo) with differing metastatic propensity were examined. C8161 showed a 2- to 14-fold higher ability to invade reconstituted basement membrane barriers in the MICS and correspondingly high type-IV collagenase mRNA levels and collagenolytic activity, as compared with other melanoma cell lines. Likewise, differential adhesion to immobilized RBM or HUVEC monolayers was observed, but did not correlate to rank orders of malignant properties. Recently, a correlation between surface expression of ICAM-1 and secondary tumor formation by human melanomas has been described in several laboratories. Basal levels of ICAM-1 on C8161, A375 and MeWo human melanomas were compared, but no correlation with metastatic potential was noted. Proto-oncogene expression in C8161 cells was compared with A375P and A375M variants using Northern blot analysis. c-myc expression was 6-fold greater than both A375 variants; c-fos expression was 3.4-fold less than A375P and 1.7-fold less than A375M; c-jun in C8161 cells was 2.5-fold and 2.1-fold greater than expression in A375P and A375M, respectively. Because C8161 is so highly malignant, amenable to experimental manipulation, and its behavior in nude mice mimics the clinical course of malignant melanoma, this cell line will prove valuable for studying properties associated with human melanoma tumor progression.