DEFECTIVE TERMINAL DIFFERENTIATION IN CULTURE AS A CONSISTENT AND SELECTABLE CHARACTER OF MALIGNANT HUMAN KERATINOCYTES
DEFECTIVE TERMINAL DIFFERENTIATION IN CULTURE AS A CONSISTENT AND SELECTABLE CHARACTER OF MALIGNANT HUMAN KERATINOCYTES
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DOI：
10.1016/0092-8674(80)90373-6
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发表时间：
1980-01-01
期刊：
影响因子：
64.5
通讯作者：
BECKETT, MA
中科院分区：
文献类型：
--
作者：
RHEINWALD, JG;BECKETT, MA
培养条件可以改变角质形成细胞（分层鳞状上皮细胞）最终分化的速率。当在半固体培养基中被剥夺锚定时，正常的人角质形成细胞在3小时的半时间内不可逆地失去了在表面培养中重新开始生长的能力，然后开始形成角质包膜。我们检测了6株来自人类鳞状细胞癌（SCC）的细胞系是否存在这种功能缺陷。一个在半固体培养基中逐渐生长的SCC系不能诱导形成锥形包膜。另外5个在半固体培养基中生长失败的品系，在这种条件下形成包膜，但速度低于正常水平。在锚固剥夺期间，SCC细胞系的分化速度比正常情况要慢得多，在24-144小时的t1/2秒内。SCC细胞在触发终末分化方面至少存在部分缺陷。在体内，这种改变可能通过逃避限制生长的重要组织特异性机制而允许恶性行为。在培养中，半固体培养基中存活率增加的表型可用于检测和选择恶性转化的角质形成细胞。
Culture conditions can be manipulated to vary the rate at which keratinocytes (stratified squamous epithelial cells) become committed to differentiate terminally. When deprived of anchorage in semi-solid medium, normal human keratinocytes irreversibly lose the ability to reinitiate growth in surface culture with a t1/2 [half time] of 3 h and then proceed to form cornified envelopes. Six established lines from human squamous cell carcinomas (SCC) were examined for defects in this function. One SCC line which grew progressively in semi-solid medium could not be induced to form cornified envelopes. The other 5 lines, which grew abortively, at best, in semi-solid medium, formed envelopes under this condition but at subnormal rates. During anchorage deprivation the SCC lines became committed to differentiate much more slowly than normal, with t1/2''s of 24-144 h. SCC cells possess at least a partial defect in the triggering of terminal differentiation. In vivo, such an alteration may permit malignant behavior by evading an important tissue-specific mechanism for limiting growth. In culture, the phenotype of increased survival in semi-solid medium may be used to detect and select malignantly transformed keratinocytes.