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

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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