Abstract 5342: FC-IBC-02: A new in vitro-in vivo model of inflammatory breast cancer (IBC)

Abstract

Abstract Inflammatory breast cancer (IBC) is the most aggressive type of advanced breast can[[Unsupported Character - Codename ­]]cer and it is associated with a poor prognosis in spite of appropriate multidisciplinary treatments. The disease is characterized by peculiar molecular and clinical features and usually affects younger patients, mostly under the age of 50 years at diagnosis. IBC has shown the capacity to spread early, primarily through lymphatic channels and secondarily through blood vessels causing the inflammatory signs and development of early metastasis. The high incidence of metastatic disease at presentation, the persistence of residual disease after induction chemotherapy associated with significant risk of disease recurrence immediately surgery strongly support our hypothesis that these patients develop micro metastatic disease early in the disease course (Cristofanilli et al., Cancer 2007;110:1436-44). Moreover, the lower survival rate of IBC patients may be due to the early activation of metastatic process associated with a peculiar phenotype of cancer stem cells (CSCs) (Cristofanilli et al., Oncologist 2003;8:141-8). Although IBC research has been ongoing for over 15 years, very few molecular alterations have been associated specifically with IBC and few preclinical models are currently available to evaluate the peculiar biology of IBC. The majority of IBC studies have been performed using the cell lines SUM149 and SUM 190 which were developed from the primary tumor and, KPL-4 isolated from the pleural effusion of IBC patients. Although both the SUM149 and KPL-4 injected into immuno- compromised mice form primary tumors, there are currently only two in vivo xenograft models of IBC, the Mary-X and the WIBC-9 models that recapitulate the tumor emboli that are the signature of IBC in humans. We have developed another IBC model, FC-IBC-02, derivate from the pleural effusion of a 49 years old IBC triple negative patient. Tumor cells from the pleural effusion were ER(-) Pgr(-) and Her2(-) and strongly positive for tetraspanin CD151 and E-cadherin. Cells from the pleural effusion of this patient were growth under non-adherent conditions in serum-free mammary epithelial growth medium (MEGM). These tumor spheroids have Aldhehyde Dehydrogenase 1 (ALDH-1) activity and characteristics of cancer stem cells (CSC) and they rapidly developed tumors when they were injected in the mammary fat pad of SCID mice. These tumors were poorly differentiated carcinomas ER-negative PgR-negative Her2-negative and the mice developed micro metastasis in the lungs. In contrast, cells isolated under adherent conditions were unable to produce tumor in SCID mice. In summary, our studies demonstrated that IBC is a disease enriched for cells with a stem cell phenotype and these cells are highly tumorigenic. IBC may represent an ideal model to evaluate stem cell targeting therapeutic modalities. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5342. doi:1538-7445.AM2012-5342