Lung metastasis model

Kjonniksen, L, Storeng, R., Pihl, A., McLemore, T. L., and Fodstad, O. (1989). A human tumor lung metastasis model in athymic nude rats. Cancer. Res. 49, 5148-5152. 

In addition, DE-310 (qdxl) exhibited potent antitumor effects against human tumor xenografts in mice, and also significantly prolonged survival in the lung metastasis model (3LL) and in the liver metastasis model (M5076). 

Ren, C., Kumar, S., Chanda, D., Kallman, L., Chen, J., Mountz, J. D., and Pormazhagan, S. 2008. Cancer gene therapy using mesenchymal stem cells expressing interferon-beta in a mouse prostate cancer lung metastasis model. Gene Titer, 15,1446-53. 

Walser TC, Rifat S, Ma X, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res 2006 66 7701-7707. 

The peptide CXCR4 antagonist TN14003 has demonstrated antitumor efficacy in two animal models of metastatic breast and head and neck cancer [48, 103]. Animals were treated with the CXCR4 peptide by intraperitoneal injection for 35 days. Tumors at the primary subcutaneous site of injection as well as the number of lung metastasis were inhibited. In the head and neck animal model, antitumor activity was correlated with anti-angiogenic activity of the anti-CXCR4 treatment. 

Taking these factors into consideration, the intravenous administration of Hpoplex may represent a promising gene dehvery method to treat pulmonary diseases. Simple gene delivery can be an effective approach for the treatment of lung diseases, including pulmonary metastasis of tumor cells. Indeed, the intravenous administration of interferon (IFN)-/9- and interleukin (IL)-12-encoding pDNA has been shown to provide effective treatment in a murine pulmonary cancer metastasis model [27, 28]. 

Walser, T.C., Rifat, S., Ma, X.R., Kundu, N., Ward, C., Goloubeva, O., Johnson, M.G., Medina, J.C. et al. (2006) Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic hreast cancer. Cancer Research, 66, 7701-7707. 

The most common application of BLI in cancer research is the use of stably transfected, luciferase expressing mmor cell lines where the luciferase signal is used as a measure of tumor burden and metastasis (55). The first example of this approach used the human cervical carcinoma cell line, HeLa (56,57). HeLa cells labeled with luciferase were injected into severe combined immunodeficient mice via the tail vein, and cells were immediately apparent in the lung. This model has since been used to examine lung colonization by several tumor cell lines. These, and now many other studies, have demonstrated that luciferase expression correlates with tumor burden through the use of many ex vivo assays and through the use of other imaging modalities (25,56,57). 

Immunohistochemical studies relate polysialic acid-NCAM expression to tumor malignancy in neuroblastoma, alveolar rhabdomyosarcoma [189], neuroendocrine lung tumors [190], Wilm s tumor [191], aggressive colon cancers [192], and pancreatic cancer [193]. In studies on the role of polysialic acid in tumor cell behavior, endosialidase has been used as a tool to remove polysialic acid from the surface of cells and tumors. In a metastasis model using human rhabdomyosarcoma TE671 cells, endoNA injected intraperitoneally reduces the expression of polysialic acid and the number of lung and liver metastases formed from intraperi-toneal primary tumors [194]. For comparison, the effect was not seen with intramuscular primary tumors that cannot be reached by the intraperitoneally injected endosialidase. 

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