Yoon S, Zhang R, Bucana C, Fidler I
UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,HOUSTON,TX 77030.
Int J Oncol. 1995 Dec;7(6):1261-7. doi: 10.3892/ijo.7.6.1261.
We examined whether the organ microenvironment modulates the response of the human lung adenocarcinoma cell line DMS-4C to doxorubicin (DXR). DMS-4C cells were injected intrathoracically (orthotopic) and subcutaneously (ectopic) into nude mice. The mice were given intravenous (i.v.) injections of DXR (8 mg/kg) or saline (control) on days 50 and 58 after implantation, Tumors growing in the subcutis were more sensitive to DXR than tumors growing in the lung. Tumor cells established in culture from lung lesions were initially more resistant to DXR than cells established in culture from subcutaneous (s.c.) tumors. After 14 days in culture, all cells exhibited similar sensitivity to DXR. The expression level of several genes that regulate different steps of metastasis, basic fibroblast growth factor (angiogenesis), type IV collagenase (invasion), epidermal growth factor receptor (growth), and mdr1 (drug resistance), was examined by an in situ mRNA hybridization technique in DMS-4C lesions from the lung and subcutis. Higher mRNA expression for Mdr1, bFGF, and type IV collagenase was found in lung lesions than in s.c. tumors. These results demonstrate that the organ environment influences the expression of several metastasis-related genes in human lung adenocarcinoma cells.
我们研究了器官微环境是否会调节人肺腺癌细胞系DMS-4C对阿霉素（DXR）的反应。将DMS-4C细胞经胸腔内（原位）和皮下（异位）注射到裸鼠体内。在植入后第50天和第58天，给小鼠静脉注射（i.v.）DXR（8mg/kg）或生理盐水（对照）。皮下生长的肿瘤比肺内生长的肿瘤对DXR更敏感。从肺部病变培养建立的肿瘤细胞最初比从皮下（s.c.）肿瘤培养建立的细胞对DXR更具抗性。培养14天后，所有细胞对DXR表现出相似的敏感性。通过原位mRNA杂交技术检测了调节转移不同步骤的几个基因，即碱性成纤维细胞生长因子（血管生成）、IV型胶原酶（侵袭）、表皮生长因子受体（生长）和mdr1（耐药性）在来自肺和皮下的DMS-4C病变中的表达水平。在肺部病变中发现Mdr1、bFGF和IV型胶原酶的mRNA表达高于皮下肿瘤。这些结果表明，器官环境会影响人肺腺癌细胞中几个转移相关基因的表达。
