Development of functional models for micrometastasis research: Linking descriptive characteristics of disseminated cancer cells to functional properties

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This collaboration within DFG/NWO was initially established to detect genetic alterations in early disseminated tumor cells (DTC) that indicate the malignant source of these cells, might enable risk stratification for metastatic relapse and could characterize putative metastatic stem cells. From our own recent work and that of other groups the picture emerged that immature breast cancer cells (i.e., cells not having all the genetic alterations that are found in the mature primary tumor) can already disseminate via the blood to secondary organs (in particular bone marrow), survive in the new microenvironment and eventually progress to overt metastatic lesions independent from the primary tumor. Thus, tumor cell dissemination can be a very early event in breast cancer development, whereas in head and neck cancer it seems to be a later event following successful establishment of lymph node metastases. In the second funding period we will investigate this challenging concept by comparing DTC in bone marrow with autologous tumor cells at the primary site or in lymph nodes from the same patient, using breast and head and neck cancer as epithelial tumors with opposing metastatic behavior. To link the descriptive characteristics of DTC to their functional properties, cell lines will be established and used as models. The findings of this project may provide new insights into the biology of DTC with implications for therapeutic approaches aimed to eliminate these cells in order to prevent overt metastasis.