Induction of Invasive Growth in a Gallbladder Cancer Cell Line by Hepatocyte Growth Factor in vitro
Induction of Invasive Growth in a Gallbladder Cancer Cell Line by Hepatocyte Growth Factor in vitro
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肝细胞生长因子体外诱导胆囊癌细胞系侵袭性生长
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发表时间：
1995
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影响因子：
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通讯作者：
Masao Tanaka
中科院分区：
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作者：
H. Shimura;Kazuhiko Date;Kunio Matsumoto;Toshikazu Nakamura;Masao Tanaka
为了研究胆囊癌细胞的侵袭和转移机制，我们从胆囊低分化腺癌的转移淋巴结中建立了一个癌细胞系GB‐d1。GB‐d1细胞在培养皿培养中增殖良好，在含有10%胎牛血清的胶原凝胶中形成小囊细胞团。人胚胎肺成纤维细胞（HEL）的条件培养基在培养皿中刺激GB‐d1细胞的增殖并诱导细胞散射。在凝胶培养中，条件培养基诱导球形簇转化为具有管状突起的树形菌落，模仿癌细胞侵入周围组织。在培养基中加入10 ng/ml的人重组肝细胞生长因子（h‐rHGF）时，也获得了类似的结果。h - rHGF抗血清可抑制条件培养基诱导的细胞增殖和形态学改变。HEL和人胆囊间质成纤维细胞样细胞在培养基中产生大量的HGF，而GB‐d1不产生任何可检测到的HGF。这些结果提示HGF促进了体外胆囊癌细胞的侵袭性生长，也提示间质成纤维细胞可能在胆囊癌的侵袭性进展中以旁分泌方式发挥重要作用。
To study the mechanism of invasion and metastasis of gallbladder cancer cells, we established a cancer cell line, GB‐d1, from a metastatic lymphnode of poorly differentiated adenocarcinoma of the gallbladder. GB‐d1 cells proliferate well in a dish culture and form small cystic cell clusters in a collagen gel containing 10% fetal bovine serum. A conditioned medium of human embryonic lung fibroblasts (HEL) stimulated the proliferation of GB‐d1 cells and induced cell scattering in the dish culture. In the gel culture, the conditioned medium induced a transformation of the spherical clusters to arborizating colonies with tubular projections that mimicked an invasion of cancer cells into the surrounding tissue. Similar results were obtained when 10 ng/ml of human recombinant hepatocyte growth factor (h‐rHGF) was added to the culture medium. The proliferative and morphological changes induced by the conditioned medium were inhibited by antiserum against h‐rHGF. HEL and human gallbladder stromal fibroblast‐like cells produced substantial levels of HGF in the culture media, while GB‐d1 did not produce any detectable level of HGF. These results suggest that HGF promotes the invasive growth of gallbladder cancer cells in vitro, and it was also suggested that stromal fibroblasts may play an important role in the invasive progression of gallbladder cancer in a paracrine fashion.