Tumor heterogeneity and tumor-host interactions as prognostic markers in breast cancer

• Grant number: 10/16684-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2011
• End date: July 31, 2012
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Auro del Giglio
• Grantee: Anna Estela Luiza Coló
• Host Institution: Instituto Israelita de Ensino e Pesquisa Albert Einstein (IIEPAE). Sociedade Beneficente Israelita Brasileira Albert Einstein (SBIBAE). São Paulo , SP, Brazil

Abstract

The mechanisms of cancer metastasis are unclear and probably this is the reason why the current prognostic markers are not effective. The formation of metastasis requires the migration of tumor cells from the primary sites to other organs. Therefore, the detection of circulating tumor cells (CTC) would be useful to assess metastasis risk. However, the cells within a tumor mass present great heterogeneity and it has been proposed that only a subpopulation of them, the cancer initiating cells (CIC), have metastatic capacity. In addition to CTC, studies on mechanisms of metastasis suggest evidences of interaction between the host organism and the tumor. In murine models, intradermal injection of tumor cell lines was followed by the migration of heamatopoietic bone marrow progenitor cells (HBMPC) to the lung and formation of clusters. After that, the tumor cell line joined spontaneously the HBMPC, indicating that the tumor triggers the migration of cells from the bone marrow to other tissues and the formation of niches. On the other hand, it is possible that the HBMPC also attract CTC. Thus, we hypothesized that the patients with greater risk of developing metastasis are those with higher quantities of CTC, CICC and/or HBMPC. Therefore, the goal of this study is to detect CTC, CICC and HBMPC and to associate them to cancer progression. These findings would suggest that cancer is a systemic disease, even if it is not considered disseminated according to current understanding, once it interacts with the whole organism. This concept would allow the establishment of new approaches for the prevention of metastasis.