Dorsal Skin Of Nude Mice Research Articles

Perspektiven HER-2 blockierender Therapiestrategien im Mausmodell: Rasche Tumorremission in Abhängigkeit vom Tumorstadium, aber keine dauerhafte Heilung

Purpose: HER-2 blocking strategies, for instance with trastuzumab (Herceptin®), have been successfully used in therapy of breast cancer. To study molecular mechanisms and the efficiency of HER-2 blocking therapies we established a mouse tumor model that allows switching-off of HER-2 expression in tumor tissue. Material and Methods: NIH3T3 cells conditionally expressing HER-2 by the TET-OFF system (NIH3T3-HER-2 cells) were subcutaneously injected into the dorsal skin of nude mice. These cells allowed switching-off of HER-2 expression by exposure to anhydrotetracycline. We examined the influence of HER-2 down-regulation on tumor volume of subcutaneously growing tumors in nude mice. Tumor development was studied by magnetic resonance imaging. HER-2 expression was quantified by Western Blot analysis. Results: Eight to ten days after injection of 7 × 10 6 NIH3T3-HER-2 cells small subcutaneously growing tumors became visible. A surprisingly efficient tumor remission was observed already 7 days after switching-off of HER-2 expression: mice with initial tumor volumes of 0.8, 1.2, 3.9 and 14.9 cm 3 showed a decrease in tumor volumes to 1.9, 11.8, 11.3 and 25.8%, respectively, compared to the respective volumes before anhydrotetracycline administration. In contrast, a steady increase in tumor volume was observed for mice not exposed to anhydrotetracyclin. Conclusion: Switching-off of HER-2 expression causes a strong remission already after 7 days. Interestingly, the extent of tumor remission depends on initial tumor size, whereby a stronger remission can be achieved for smaller tumors. Our data support clinical studies testing HER-2 blocking strategies as adjuvant therapy for early breast cancer.

Analysis of the biological properties and use of comparative genomic hybridization to locate chromosomal aberrations in the human testicular seminoma cell line JKT-1 and its highly metastatic cell line JKT-HM.

To examine the biological properties, and utility of comparative genomic hybridization (CGH) to locate chromosomal aberrations, in a new human testicular seminoma cell line, JKT-1, and a highly metastatic cell line, JKT-HM, developed as an animal model of spontaneous metastasis. JKT-HM was isolated by transplanting cells of JKT-1 into the dorsal skin of nude mice, using methods developed previously. The biological properties of JKT-1 and JKT-HM cells were examined using assays of cell proliferation and in vitro tumour cell invasion, and the DNA index (by flow cytometry). CGH was used to analyse chromosomal aberrations and to detect chromosomal regions causing metastasis in the testicular seminoma cell lines. The JKT-1 and JKT-HM cells showed no difference in morphology or cell proliferation. After transplanting JKT-HM into mice, the cells metastasized to the lung and lymph nodes in all five mice by 50 days. The in vitro tumour cell invasion and animal assays suggested potential invasion and metastasis of JKT-HM. The DNA index was 1.48 for JKT-1 and 1.50 for JKT-HM. CGH analysis revealed various chromosomal aberrations undetected by examining their karyotypes, e.g. loss of 18p, Yq and gain of Xq, and the technique has potential to detect genetic aberrations related to metastasis in this model. The two cell lines JKT-1 and JKT-HM, and the metastatic animal model used, were useful in studying human testicular seminoma and the metastatic behaviour of cancer. In addition, CGH was useful for analysing the chromosomes of two different cell lines derived from the same parent line.