Studies of human breast cancer metastasis using nude mice

Abstract

Athymic nude mice have been used in recent years to study the biology of human tumors and to assess therapeutic responses in vivo rather than just in vitro. Some human tumors metastasize in nude mice, providing model systems for analyzing various aspects of the metastatic phenotype of human neoplasms. For breast carcinomas, however, the tumor-take rate of surgical specimens is low, and only a limited number of cell lines proliferate in nude mice. The site of injection of the breast carcinoma cells is important; tumors grow at a lower inoculum dose and with shorter latent intervals after implantation in the mammary fatpad of nude mice than after injection in the subcutis. One breast carcinoma cell line, MDA-MB-435, metastasizes from mammary fatpad tumors to lymph nodes, lungs, and other visceral organs. In contrast, two other cell lines show lower metastatic ability. Intravenous injection and injection of tumor cells into the internal carotid artery of nude mice produces lung and brain metastases, respectively, thus simulating the arrest and organ colonizing steps of the metastatic cascade. These different techniques demonstrate the potential of experimental studies of human breast cancer growth and metastasis using nude mice.

Alterations of the HBP1 Transcriptional Repressor Are Associated with Invasive Breast Cancer

“…B, nonparametric ANOVA analysis of HBP1 mRNA expression. HBP1 levels for normal (25)(26)(27)(28)(29)(30)(31)(32)(33) in top ), all invasive (1-23), invasive-low HBP1 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), and invasive-high HBP1 (17-23) were compared by nonparametric ANOVA. Dunn's multiple comparisons test was then used.…”

“…Therefore, we assessed the consequences of an HBP1 knockdown on invasiveness and proliferation of MDA-MB-231 cells. These cells remain an established model for invasion and for tumorigenic proliferation studies, including anchorage-independent growth and tumor formation in orthotopic xenograft models (30,31). As shown in Fig.…”

Pharmacodynamic Behavior of Liposomal Antisense Oligonucleotides Targeting Her-2/neu and Vascular Endothelial Growth Factor in an Ascitic MDA435/LCC6 Human Breast Cancer Model

“…An associated correlate to this ideal is that the model used should also mimic the human disease state or condition. The MDA435/ LCC6 ascites tumor model is a direct derivative of the estrogen receptor negative, invasive and metastatic MDA-MB-435 cell line [34][35] and has been characterized as such by isotype and karyotype analysis. 20 It has been suggested that the coexpression of molecular markers in neoplastic transformation functions as a significant prognostic correlate for recurrence, and that the number of coexpressed markers is directly related to this significance.…”

Development of a new metastatic human breast carcinoma xenograft line

“…At present, numerous breast carcinoma cell lines established from primary solid human breast carcinoma or from the metastatic pleural fluids are available for various research (Nordquist et al, 1975;Engel and Young, 1978;Langlois et al, 1979;Whitehead et al, 1983;Chu et al, 1985;Mehta et al, 1992;1995b;Watanabe et al, 1992;Slooten et al, 1995); however, only a limited number of these cell lines are tumorigenic in mice, and only two to three of these cell lines show distant metastasis when transplanted s.c. into athymic mice (Shafie and Liotta, 1980;Price et al, 1990;Brunner et al, 1992;Mehta et al, 1993). In addition the incidence of metastasis in these cell lines varies in different laboratories (Shafie and Liotta, 1980).…”

“…In most cases, xenografts originated in vivo in experimental animals preserve many of the original phenotypic, biological and genotypic characteristics from which they originate (Giovanella et al, 1989;Mehta et al, 1995a). However, human breast carcinomas are difficult to grow in vitro in culture (Nordquist et al, 1975;Engel and Young, 1978;Langlois et al, 1979;Whitehead et al, 1983;Chu et al, 1985;Mehta et al, 1992; 1995b ;Watanabe et al, 1992) or in vivo in experimental animals (Sabestany et al, 1979;Shafie and Liotta, 1980;Rae-Venter and Reid, 1980;Giovanella et al, 1985;Price and Zhang, 1990;Hurst J, et al, 1993;Mehta et al, 1993), and they rarely metastasize when transplanted subcutaneously (Shafie and Liotta, 1980;Price et al, 1990;Brunner et al, 1992;Mehta et al, 1993).…”