Abstract 3358: Acquired epithelial-mesenchymal transition synergizes with normal epithelial cells to induce hepatic metastases

• Published in: Cancer research (Chicago, Ill.) Ill.), 2011-04, Vol.71 (8_Supplement), p.3358-3358
• Main Authors: Zubeldia, Idoia G., Bleau, Anne-Marie, Gil-Puig, Carmen, Vidal-Vanaclocha, Fernando, Calvo, Alfonso, Lecanda, Jon
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-3358

Identification of the required hallmarks for the tumor cells to disseminate to the liver represents an important milestone to delay cancer progression, and consequently to avoid the harmful consequences for patients. Largely unknown, a myriad of cell properties seem to cooperate in a successful metastatic process and in the chemo-/radio- therapeutic resistance. Our aim is to define the intrinsic characteristics of tumor cells that may contribute to epithelial-mesenchymal transition (EMT) in early and late metastatic events. We previously observed that: i) metastatic cells reaching the liver microenvironment display cancer stem features associated with EMT and increased TGFβ1-signaling (Zubeldia et al. Proceedings AACR, 2010; 51, #2304); ii) hepatic secondary tumors are enriched with a subpopulation of cells with a distinctive Sca1+ phenotype and a concurrent increased expression of other cancer stem markers (Zubeldia et al. Proceedings MRS-AACR, 2010; #A105). First, we demonstrated the high tumorigenicity of these metastatic liver-derived cell lines after subcutaneous injection in nude mice, without obvious correlation with their origin regarding TGFβ1-signaling. However, as shown by bioluminescent imaging, some of the novel metastatic liver-derived cell sublines were unable to achieve metastases following intrasplenic injection in C57BL/6J mice. We also noted a differential efficiency of each clone in primary tumor formation in this experimental model. Importantly, we found that co-injection of these cells (isolated from liver metastases) with non transformed hepatocytes (AML12) resulted in a significant increase of metastasis formation. We show an important role of normal cells for metastatic spread in early steps of tumor formation, and suggest the protective activity that the untransformed epithelial cells may have throughout the metastatic progression. We will present the therapeutic implications of our findings for the clinical treatment of carcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3358. doi:10.1158/1538-7445.AM2011-3358