Abstract 3321: From mouse to humans: detecting preventing vaccination targets associated to breast cancer stem cells
Authors: Lanzardo Stefania , Conti Laura , Forni Guido , Cantarella Daniela , Cavallo Federica , Calogero Raffaele A. 
Published: February 2011

The characterization of genes differentially expressed during the stages of tumorigenesis may lead to the identification of prominent pathways and molecules against which to trigger an immune response. We have coined the term “oncoantigens” for tumor-associated molecules which play important roles in driving the progression of a neoplastic lesion from one stage to the next. We have identified putative oncoantigens (POAs) to be targeted by preventive vaccination as molecules already expressed by mammary cells in pre-neoplastic lesions and over-expressed in mammary cells of overt neoplastic lesions. However, many human malignancies, including breast cancer, are organized in a hierarchical network of rare, slowly dividing cancer stem cells (CSCs). The CSC hypothesis suggests that CSCs are not only the source of the tumor but could be responsible for tumor progression, metastasis, resistance to therapy and tumor recurrence. If only a small fraction of cells is capable of initiating cancer, preventive vaccination should be designed to target these rare CSCs. Therefore an analysis of CSCs transcriptional profiling may unravel novel POAs which are more suitable for effective preventive vaccination.

To do this, mammary tumor specimens were obtained from a cell line derived from a BALB-neuT mammary carcinoma. Cells were plated in differentiated conditions in order to obtain adherent tumor epithelial cells (e0) and under conditions in which they cannot attach to a solid substratum to obtain mammospheres (p1). The latter we have previously reported as showing clonogenicity, self renewal and ability to differentiate in epithelial/myoepithelial cells of the mammary gland and to maintain tumorigenic potential. The mammospheres generated were disaggregated and plated to obtain second (p2) and third (p3) passage mammospheres. Transcription profiling was performed on e0, p1-3 using Affymetrix Exon 1.0 ST Mouse arrays. A total of 452 deregulated transcripts were detected using rank product statistics, comparing e0 with respect to p1-3. Since we are interested in detecting CSC vaccination targets, we selected by clustering a subset of 183 transcripts (POAs), characterized by an increasing expression trend from passage p1 to p3. Four of them could be linked to known staminality markers by IPA analysis. Furthermore, we ranked POAs on the basis of the relationship between expression and distance recurrence in 7 publicly available human breast cancer transcription profile studies. The presence of specific transcript isoforms associated to CSC is actually under investigation. POAs will be validated as vaccine in our preclinical model of mammary carcinogenesis.

Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3321.