Ahn K S, Jung Y S, Kim J, Lee H, Yoon S S
Department of Hematooncology, SungKyunKwan University, School of Medicine, Seoul, Republic of Korea.
Tumour Biol. 2001 May-Jun;22(3):146-53. doi: 10.1159/000050609.
We examined whether the organ microenvironment modulates the metastatic behavior and the response to doxorubicin (DXR) in murine renal carcinoma (RENCA) cells. Tumor cells were injected into kidney (orthotopic) and subcutis (ectopic) of syngeneic mice. Lung metastases developed in up to 57% (17/30) of animals having kidney tumors but not in those with skin tumors. Tumors growing in the kidney were more resistant to DXR than tumors growing in the subcutis when mice were given intravenous injections of DXR (8 mg/kg) on days 8 and 15 after implantation. In addition, tumor cells cultured from kidney tumors were initially more resistant to DXR than tumor cells cultured from subcutis tumors. After tumor cells were passaged in vitro, all cells exhibited a similar sensitivity to DXR. Additionally, we examined the expression levels of mdr1, EGFR and type IV collagenase by an in situ mRNA hybridization technique. A higher mRNA expression for type IV collagenase and EGFR was found in kidney tumors than in subcutis tumors. These results demonstrate that the organ environment influences the drug responsiveness and the expression of metastasis-related genes in murine renal carcinoma cells.
我们研究了器官微环境是否会调节小鼠肾癌细胞（RENCA）的转移行为以及对阿霉素（DXR）的反应。将肿瘤细胞注射到同基因小鼠的肾脏（原位）和皮下（异位）。在患有肾肿瘤的动物中，高达57%（17/30）出现了肺转移，而患有皮肤肿瘤的动物则未出现肺转移。当在植入后第8天和第15天给小鼠静脉注射DXR（8mg/kg）时，生长在肾脏中的肿瘤比生长在皮下的肿瘤对DXR更具抗性。此外，从肾肿瘤培养的肿瘤细胞最初比从皮下肿瘤培养的肿瘤细胞对DXR更具抗性。肿瘤细胞在体外传代后，所有细胞对DXR表现出相似的敏感性。此外，我们通过原位mRNA杂交技术检测了mdr1、EGFR和IV型胶原酶的表达水平。在肾肿瘤中发现IV型胶原酶和EGFR的mRNA表达高于皮下肿瘤。这些结果表明，器官环境会影响小鼠肾癌细胞的药物反应性和转移相关基因的表达。
