Adhesion molecules and TGF‐β1 are involved in the peritoneal dissemination of NUGC‐4 human gastric cancer cells
Adhesion molecules and TGF‐β1 are involved in the peritoneal dissemination of NUGC‐4 human gastric cancer cells
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粘附分子和TGF-β1参与NUGC-4人胃癌细胞的腹膜播散
DOI：
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
R. Kannagi
中科院分区：
文献类型：
--
作者：
T. Nakashio;T. Narita;S. Akiyama;Y. Kasai;K. Kondo;Katsuki Ito;H. Takagi;R. Kannagi
胃癌患者术后常发生腹膜播散。手术后腹膜转移的存在影响预后。目前对胃癌细胞与腹膜间皮细胞最初粘附的生化过程知之甚少。我们进行了体外和体内研究，以评估粘附分子和TGF-β1在这一过程中的作用，使用4种来源于人胃癌的细胞系。NUGC-4细胞在接种到裸鼠腹腔后早期播散，主要表达CD 44 H和β1整联蛋白。我们发现NUGC-4细胞与间皮细胞单层的粘附比其他细胞系更牢固。NUGC-4细胞与间皮细胞的粘附被抗CD 44 H或整联蛋白β1亚基的抗体部分抑制，并被这2种抗体的组合完全阻断。用CD 44 H和β1整联蛋白的配体处理也抑制粘附。在NUGC-4细胞培养基中，与其他细胞系相比，检测到与癌细胞增加相关的更大量的TGF-β1。TGF-β1增加了NUGC-4细胞和间皮细胞中CD 44 H的表达，并增强了NUGC-4细胞与间皮细胞的粘附和植入，伴随着细胞外基质（ECM）成分的积累。用抗CD 44 H和β1整合素的抗体治疗可抑制NUGC-4细胞在裸鼠腹腔中的播散，并延长其存活时间。我们的研究结果表明，CD 44 H和整合素介导胃癌细胞与间皮细胞的初始附着，TGF-β1参与了疾病的促进。TGF-β1诱导的CD 44 H表达增加以及CD 44 H配体和整合素的量增加促进腹膜播散的早期发展。Int. J. Cancer 70：612-618.© 1997 Wiley利斯公司
Peritoneal dissemination frequently occurs after surgery in patients with gastric cancer. The presence of peritoneal metastasis after surgery affects prognosis. Very little is known about the biochemical processes involved in the initial attachment of gastric cancer cells to peritoneal mesothelial cells. We conducted in vitro and in vivo studies to assess the role of adhesion molecules and TGF‐β1 in this process, using 4 cell lines derived from human gastric cancers. NUGC‐4 cells, which disseminate early after inoculation into the abdominal cavity of nude mice, predominantly express CD44H and β1 integrin. We found that NUGC‐4 cells adhered to monolayers of mesothelial cells more firmly than to other cell lines. Adhesion of NUGC‐4 cells to mesothelial cells was partially inhibited by antibodies against CD44H or the β1 subunit of integrin and was completely blocked by a combination of these 2 antibodies. Treatment with ligands for CD44H and β1 integrin also inhibited adhesion. In the NUGC‐4 cell culture medium, larger amounts of TGF‐β1 were detected in relation to the increase in cancer cells than in the other cell lines. TGF‐β1 increased the expression of CD44H in NUGC‐4 cells and in mesothelial cells and augmented adhesion and implantation of NUGC‐4 cells to mesothelial cells accompanied by accumulation of extracellular matrix (ECM) components. Treatment with antibodies against both CD44H and β1 integrin inhibited the dissemination of NUGC‐4 cells in the peritoneal cavity of nude mice and prolonged their survival time. Our findings suggest that CD44H and integrins mediate the initial attachment of gastric cancer cells to mesothelial cells and that TGF‐β1 participates in the promotion of the disease. Increased expression of CD44H and of the amount of ligands for CD44H and integrins induced by TGF‐β1 promotes early development of peritoneal dissemination. Int. J. Cancer 70:612–618. © 1997 Wiley‐Liss Inc
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DOI：
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发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
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作者：
R. Ignotz;J. Massagué
通讯作者：
R. Ignotz;J. Massagué
影响因子：
11.2
作者：
Stephen A. Cannistra;G. Kansas;J. Niloff;B. DeFranzo;Young Ho Kim;Christian H. Ottensmeier
通讯作者：
Stephen A. Cannistra;G. Kansas;J. Niloff;B. DeFranzo;Young Ho Kim;Christian H. Ottensmeier
DOI：
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发表时间：
1993
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
S. Albelda
通讯作者：
S. Albelda
DOI：
10.1016/s0021-9258(18)69173-2
发表时间：
1988-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Bassols;J. Massagué
通讯作者：
A. Bassols;J. Massagué