TGF-ALPHA CAN ACT AS MORPHOGEN AND/OR MITOGEN IN A COLON-CANCER CELL-LINE
TGF-ALPHA CAN ACT AS MORPHOGEN AND/OR MITOGEN IN A COLON-CANCER CELL-LINE
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DOI：
10.1002/ijc.2910560423
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发表时间：
1994-02-15
影响因子：
6.4
通讯作者：
PIGNATELLI, M
中科院分区：
文献类型：
--
作者：
LIU, D;GAGLIARDI, G;PIGNATELLI, M
转化生长因子α (tgf - α)对多种间充质和上皮细胞具有多功能生物学作用。它是许多正常和转化细胞类型的有效丝裂原，调节细胞外基质（ECM）的产生，促进乳房，肾脏和肺的形态发生。为了阐明ECM蛋白在tgf - α的形态发生和有丝分裂作用中的作用，我们使用了表达EGF受体的人结肠癌细胞系（SW1222）。本研究表明，1 ng/ml的tgf - α可促进SW1222细胞的增殖，但仅在塑料培养皿上培养，而不是胶原涂层培养皿上培养。较高浓度的tgf - α (10 ng/ml)对细胞增殖没有促进作用，但在三维胶原凝胶中培养时，其隐窝样腺分化明显增强（p = 0.027）。这些影响伴随着α (2) β(1)和α (3) β(1)整合素分子（细胞外基质蛋白的受体）的表达增加，以及SW1222细胞与1型胶原结合的统计学显著增加。识别α (2) β(1)整合素的单克隆抗体抑制了TGF-cr与1型胶原结合和三维胶原凝胶形态分化的作用。这些数据表明，TGF-ar的形态发生或有丝分裂活性严重依赖于细胞与细胞外基质蛋白的相互作用，并主要由α (2) β(1)整合素受体介导。在细胞-基质相互作用严重受损的肿瘤中，这种生长因子的不适当表达可能对正常组织结构的维持和生长控制产生有害影响。(C) 1994 Wiley-Liss, Inc。
Transforming growth factor alpha (TGF-alpha) has multifunctional biological effects on a variety of mesenchymal and epithelial cells. It is a potent mitogen for a number of normal and transformed cell types, regulates extracellular matrix (ECM) production and promotes breast, kidney and lung morphogenesis. To clarify the role of ECM proteins in the morphogenetic and mitogenic effects of TGF-alpha, we have used a human colon carcinoma cell line (SW1222) which expresses EGF receptor. Here we show that TGF-alpha at I ng/ml increases the proliferation of SW1222 cells, but only when they ave cultured on plastic rather than collagen-coated plates. Higher concentrations of TGF-alpha (10 ng/ml) did not increase cell proliferation but significantly enhanced the crypt-like glandular differentiation when cells were grown in 3-dimensional collagen gel (p = 0.027). These effects were accompanied by increased expression of alpha(2) beta(1) and alpha(3) beta(1) integrin molecules, which are receptors for extracellular matrix proteins, and by a statistically significant increase in binding of SW1222 cells to type-1 collagen. The effects of TGF-cr both on binding to type-1 collagen and on morphological differentiation in 3-dimensional collagen gel were inhibited by monoclonal antibodies recognizing the alpha(2) beta(1) integrin. These data indicate that the morphogenetic or mitogenic activities of TGF-ar are critically dependent on cellular interactions with extracellular matrix proteins and are primarily mediated by the alpha(2) beta(1) integrin receptor. Inappropriate expression of this growth factor, seen in tumours whose cell-matrix interactions are greatly impaired, could have deleterious effects on the maintenance of normal tissue architecture and growth control. (C) 1994 Wiley-Liss, Inc.