LOSS OF RECEPTORS FOR TRANSFORMING GROWTH-FACTOR-BETA IN HUMAN T-CELL MALIGNANCIES
LOSS OF RECEPTORS FOR TRANSFORMING GROWTH-FACTOR-BETA IN HUMAN T-CELL MALIGNANCIES
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DOI：
10.1073/pnas.91.13.6002
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发表时间：
1994-06-21
影响因子：
11.1
通讯作者：
GEORGE, D
中科院分区：
文献类型：
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作者：
KADIN, ME;CAVAILLECOLL, MW;GEORGE, D
Ki-1 (CD30)(+) 皮肤 T 细胞淋巴瘤 (CTCL) 是缓慢进展的淋巴瘤，通常观察到初始自发消退。为了更好地了解 Ki-1(+) CTCL 中自发消退和最终肿瘤进展的机制，研究了 β 型转化生长因子 (TGF-β) 介导的克隆相关细胞系的生长抑制，这些细胞系源自肿瘤进展之前和之后的两次绘制。 TGF-β 1 抑制源自临床惰性 Ki-1(+) CTCL 的细胞系 (Mac-1) 的集落形成效率 (CFE)，但无法抑制源自晚期 CTCL 的 Mac-2A 和 -2B 细胞系的 CFE。为了确定晚期 CTCL 细胞中 TGF-β 1 抵抗的基础，我们寻找细胞表面 TGF-β 受体表达的可能缺陷。 Mac-1 细胞被发现表达介导生长抑制的 TGF-β 受体 I 和 II，以及 TGF-β 结合蛋白聚糖 β 聚糖。相反，在 CTCL 系 Mac-2A 和 -2B 中未检测到受体 I 和 II，即使这些细胞系确实表达 β 聚糖。在其他细胞中揭示或诱导 TGF-β 受体的各种治疗未能在晚期 CTCL 细胞中显示这些受体的证据。这些细胞中 TGF-β 受体表达的丧失与 TGF-β 受体 II mRNA 水平的显着下降相关。在其他五名 T 细胞淋巴瘤患者（包括塞扎里综合征和非皮肤 T 细胞淋巴瘤）中，也发现有两人细胞表面 TGF-β 受体缺失，这表明 TGF-β 受体表达缺失可能是人类 T 细胞恶性肿瘤的一个复发特征。
Ki-1 (CD30)(+) cutaneous T-cell lymphomas (CTCLs) are slowly progressive lymphomas in which initial spontaneous regression is often observed. To better understand the mechanisms of spontaneous regression and eventual tumor progression in Ki-1(+) CTCLs, type beta transforming growth factor (TGF-beta)-mediated growth inhibition of clonally related cell lines derived from two time paints, before and after tumor progression, was studied. TGF-beta 1 inhibited colony-forming efficiency (CFE) of a cell line (Mac-1) derived from clinically indolent Ki-1(+) CTCLs but failed to inhibit CFE of Mac-2A and -2B cell lines from advanced CTCLs. To determine the basis for TGF-beta 1 resistance in advanced CTCL cells, we looked for possible defects in the expression of cell surface TGF-beta receptors. Mac-1 cells were found to express TGF-beta receptors I and II, which mediate growth inhibition, and the TGF-beta-binding proteoglycan betaglycan. In contrast, receptors I and II were not detected in CTCL lines Mac-2A and -2B even though these cell lines did express betaglycan. Various treatments that unmask or induce TGF-beta receptors in other cells failed to show evidence for these receptors in advanced CTCL cells. Loss of TGF-beta receptor expression in these cells correlated with a marked decrease in TGF-beta receptor II mRNA levels. Loss of cell surface TGF-beta receptors was also found in two of five other patients with T-cell lymphomas including the Sezary syndrome and a noncutaneous T-cell lymphoma, suggesting that loss of TGF-beta receptor expression may be a recurrent feature of human T-cell malignancies.