Hypoxic stress reaction in breast cancer cells

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Cell stress and dissemination

Tumour cells are frequently exposed to adverse microenvironmental conditions or to rapid changes of their microenvironment. Adverse conditions may be low oxygen partial pressure (hypoxia) or low glucose levels (hypoglycaemia), while rapid changes in the microenvironment may occur when primary tumour cells disseminate to novel microenvironments at secondary organs. In both circumstances stress in the tumour cells is induced, leading to activation of special cytoprotective programs to maintain cellular functions.

In focus of our research is the settlement of disseminated breast tumour cells into the bone marrow microenvironment. This process is characterized by rapid changes of microenvironment of the tumour cells in the course of the dissemination from the primary tumour into the blood circuit and settlement in bone marrow. In addition, the hematopoietic stem cell niche of the bone marrow exhibits a low oxygen partial pressure, which may induce cell stress in tumour cells that are disseminated to this site.

Since adaptation to cell stress is a response to unphysiological conditions, it rarely occurs in normal cells. Hence, proteins of cytoprotective programs like the unfolded protein response are suitable marker proteins for the detection of tumour cells. Moreover, increased tolerance of the tumour cells against microenvironmental stress can confer tolerance against therapeutic approaches as well. In turn, identification of vulnerabilities in stress response programs may reveal structures that allow a specific targeting of those cells. Consequently, discoveries in the tumour cell stress responses can provide tools that allow the specific detection and the targeting of exceptionally resistant tumour cells.

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