Analysis of antiinvasive and antimetastatic effects of antimetasatic agents and cytotoxic drugs in a metastasis model of human breast cancer

我们最近利用MKL-4人乳腺癌细胞系建立了一种新的转移模型，该细胞系是携带成纤维细胞生长因子-4和lac-Z的MCF-7细胞系的转基因细胞。在这个模型中，用解剖显微镜可以定量观察到β-半乳糖苷酶活性染色的微转移到淋巴结和远处器官。在本研究项目中，我们取得了以下研究成果：1.从淋巴结和肺转移灶建立了亚线。MKL-4-L1是淋巴结转移亚系之一，在裸鼠体内生长较快，有较高的转移潜能。2.抗血管生成药物TNP-470抑制MKL-4裸鼠移植瘤的血管生成、生长和自发性转移。TNP-470被建议用于治疗更具侵袭性和激素非依赖性的乳腺癌。UFT是一种抗代谢药物，可抑制生长和转移。这种药物在移植的肿瘤内引起了大量的坏死。4.一种新型抗…抗体更多侵袭剂、侵袭抑制因子2在不影响原发肿瘤生长和血管生成的情况下抑制肿瘤的侵袭和自发转移。一种新开发的计算机辅助的肿瘤侵袭性分析可能有助于对体内肿瘤细胞侵袭性的定量测量。5.在该转移模型中，建议一次切除肿瘤以诱导微转移的进展。我们计划使用这种技术建立一种新的术后转移模型。此外，我们还建立了两个新的人乳腺癌细胞系KPL-1和KPL-3C。KPL-1细胞在体内和体外都能分泌大量的组织多肽抗原。有趣的是，KPL-1细胞有雌激素受体，但不依赖激素。KPL-3C细胞稳定分泌甲状旁腺激素相关蛋白。这两种细胞系在裸鼠体内都有致瘤作用。有趣的是，KPL-3C细胞在裸鼠体内产生与微钙化相关的移植瘤。这些新的细胞系可能是研究乳腺癌细胞生物学的有用研究资源。较少

We recently established a novel metastasis model using an MKL-4 human breast cancer cell line, a transfectant of MCF-7 cell line with fgf-4 and lac Z.In this model, micrometastases, which were stained for beta-galactosidase activity, into lymph nodes and distant organs can be quantitatively observed with a dissecting microscope. In this research project, we have obtained research results as follows : 1. Sublines were established from metastatic foci at lymph nodes and lungs. One of the sublines from lymph node metastases, MKL-4-L1 exhibited a more rapid growth and higher metastatic potential in nude mice. 2. An antiangiogenic agent, TNP-470 inhibited angiogenesis, growth and spontaneous metastasis of the MKL-4 cells transplanted into nude mice. TNP-470 was suggested to be useful in treating more aggressive and hormone-independent breast cancers.3. An antimetabolite, UFT inhibited growth and metastasis. This drug induced a massive necrosis inside the transplanted tumors. 4. A novel anti … More invasive agent, invasion-inhibiting factor 2 inhibited invasion and spontaneous metastasis without affecting primary tumor growth and angiogenesis. A newly-developed computer-assisted analysis of tumor invasiveness may be useful in the quantitative measurement of tumor cell invasion in vivo. 5. A primary tumor removal was suggested to induce progression of micrometastasis in this metastasis model. We have a plan to establish a new postsurgical metastasis model using this technique. In addition, we have established two new human breast cancer cell lines, KPL-1 and KPL-3C.KPL-1 cells secrete a large amount of tissue polypeptide antigens both in vitro and in vivo. Interestingly, KPL-1 cells have estrogen receptors but are hormone-independent. KPL-3C cells stably secrete parathyroid hormone-related protein. Both cell lines are tumorigenic in nude mice. Interestingly, KPL-3C cells produce transplanted tumors associated with microcalcifications in nude mice. These new cell lines may be useful research resources to investigate breast cancer cell biology. Less