Shimura H, Date K, Matsumoto K, Nakamura T, Tanaka M
Department of Surgery 1, Kyushu University Faculty of Medicine, Fukuoka.
Jpn J Cancer Res. 1995 Jul;86(7):662-9. doi: 10.1111/j.1349-7006.1995.tb02450.x.
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-HGF. 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.
为研究胆囊癌细胞侵袭和转移的机制，我们从低分化胆囊腺癌转移淋巴结建立了一个癌细胞系GB-d1。GB-d1细胞在培养皿中增殖良好，并在含10%胎牛血清的胶原凝胶中形成小的囊性细胞簇。人胚肺成纤维细胞（HEL）的条件培养基刺激GB-d1细胞增殖，并在培养皿培养中诱导细胞散射。在凝胶培养中，条件培养基诱导球形簇转变为具有管状突起的树枝状集落，模拟癌细胞向周围组织的侵袭。当向培养基中添加10 ng/ml人重组肝细胞生长因子（h-rHGF）时，也获得了类似结果。条件培养基诱导的增殖和形态学变化被抗h-HGF抗血清抑制。HEL和人胆囊基质成纤维样细胞在培养基中产生大量HGF，而GB-d1未产生任何可检测水平的HGF。这些结果表明HGF在体外促进胆囊癌细胞的侵袭性生长，也提示基质成纤维细胞可能以旁分泌方式在胆囊癌的侵袭进展中起重要作用。
