Development of a new metastatic human breast carcinoma xenograft line

Abstract

Summary Xenografts originated from human tumours offer the most appropriate research material for in vivo experimental research. However, primary human breast carcinomas are difficult to grow when transplanted in athymic mice: tumour take is less than 15%. Recently, we have achieved 60% tumour take by injecting tumour cell suspensions mixed with Matrigel. Human breast xenografts originated from primary breast carcinoma also frequently show the potential to metastasize spontaneously. In the present study, we generated a human breast carcinoma xenograft line (UISO-BCA-NMT-18) that shows 100% tumorigenicity and 80-100% lung metastasis when transplanted s.c. in athymic mice. We have studied in detail the characteristics of the xenograft and the patient's tumour from which the xenograft line originated. Both the xenograft and the patient's tumour showed intense staining for mutant p53 nuclear protein, and high expression of U-PA, PAI and u-PAR. In vivo growth of the xenograft is stimulated by exogenous supplementation of oestrogen. This xenograft is continuously growing in mice and has shown 80-100% metastasis for the last three successive in vivo passages. This well-characterized, oestrogenresponsive, metastatic breast carcinoma xenograft line will provide excellent research material for metastasis-related research.Keywords: breast cancer; xenograft; cell line; metastasis Metastasis of primary tumour to the visceral organs is a major cause of cancer-associated mortality. Despite considerable progress in the last decade in the areas of early detection and surgical and chemotherapeutic management of clinically less advanced cancers, treatment of metastatic disease is still a major puzzle for oncologists. Research on metastatic disease has severely suffered from lack of suitable experimental models. Human tumour xenografts established from well-characterized clinical material provide an important research tool for multidisciplinary research. 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).Recently, we obtained significant success in establishing xenografts from primary breast carcinomas, and many of these xenografts showed potential for spontaneous metastasis in athymic mice when transplanted s.c. (Mehta et al, 1993). Initially, we used Matrigel to develop xenografts from primary breast carci...

Efficacy and mechanism of action of Deguelin in suppressing metastasis of 4T1 cells

“…The sections were rinsed in phosphate-buffered saline (PBS) and then microwaved two times for 5 min in citrate buffer (Vector Laboratories, Burlingame, CA) for antigen retrieval. This method is described in detail previously (24). After PBS wash nonspecific staining was blocked by incubating tissue sections in 5% BSA.…”

Tumor Take Rate Optimization for Colorectal Carcinoma Patient-Derived Xenograft Models

“…They might thus be a central step towards truly patient orientated and individualized therapy [9–11]. Even models of metastatic diseases may be achieved as valuable research instruments for additional multidisciplinary research [12]. …”