Geburtshilfe Frauenheilkd 2016; 76 - P029
DOI: 10.1055/s-0036-1592967

Role of netrins and their receptors in the persistence of disseminated breast cancer cells in the human bone marrow

HC Burow 1, 2, CB Walter 1, G Klein 2
  • 1Universitätsfrauenklinik, Tübingen, Deutschland
  • 2Universitätsklinik, Innere Medizin, II, Tübingen, Deutschland

Introduction: The family of netrins is not only involved in normal tissue development, but also in different types of malignancies. In primary breast cancer there is a strong correlation between the overexpression of netrin-1 and the state of the disease and the generation of metastases. The impact on the persistence of disseminated tumor cells in the bone marrow, however, is largely unknown. In the present study we demonstrate the expression of netrins and their receptors in different cell types of the bone marrow stem cell niches and in breast cancer cells (BCC).

Methods: Netrins and their receptors were analyzed in five different BCC lines (luminal A and B, HER2-subtype, triple negative) and different cell types of the bone marrow by RT-PCR analysis, immunofluorescence stainig and Western blotting. Cell adhesion assays were used to demonstrate the involvement of netrins.

Results: Netrin-1 and netrin-4 were expressed by all BCC lines analyzed, whereas netrin-G1 and netrin-3 could not be detected. Bone marrow cells also express netrin-1 and netrin-4. The five tumor cell lines strongly attached to netrin-1. Netrin-4, in contrary, seems to have a minor adhesive function since only the most aggressive BCC line MDA-MB 231 attached to it.

Discussion: The netrin family shows a variable expression pattern in tumor cells. Netrin-1 seems to be a strong adhesive component for BCC lines, whereas netrin-4 is only a moderate adhesive substrate. Further examinations of bone marrow samples will show whether netrins and/or their receptors play a role in disseminated tumor cells of patients.