Project Details
Projekt
Bone marrow stromal cells affect cancer cell homing and growth
Applicant
Professorin Dr. Inaam Nakchbandi
Subject Area
Hematology, Oncology
Term
since 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 401246035
We are particularly interested in understanding the role of the supporting stromal cells in the development of bone metastasis and cancer progression in patients with breast and prostate cancer.Breast and prostate cancer cells can home to the bone marrow, where they presumably hijack the hematopoietic stem cell niche. They may stay dormant, but for unknown reasons sometimes start to proliferate giving rise to bone metastatic lesions. We have shown that decreasing the number of stromal cells pharmacologically enhances cancer cell homing to the bone marrow in mice. Initial characterization confirmed a relationship with two mesenchymal subpopulations, one that produces fibronectin and one that probably responds to it. We would like to define these two subpopulations further using transgenic mouse models. This will be followed by pharmacologic manipulation in mice in order to increase the identified subpopulation(s) and diminish cancer cell homing and consequently bone metastatic disease. The relevance of this population will be evaluated in bone marrow samples obtained from patients with breast and prostate cancer, and correlated with the presence of tumor cells in the bone marrow and prognosis of the disease. The ultimate aim of this part is to manipulate the stromal cells to make the premetastatic niche hostile to cancer cell, and possibly to eject them from the niche entirely.Furthermore, the bone marrow stromal cells can suppress tumor growth when injected together with tumor cells. We identified a subpopulation of stromal cells that (in contrast to other subpopulations) is able to inhibit tumor progression on its own. Here too we found another subpopulation representing 1% of the bone marrow nucleated cells that in the absence of fibronectin can no longer suppress growth. We will take advantage of transgenic models to better characterize these two subpopulations. Interestingly, an immune cell population was increased every time cancer growth was suppressed. We therefore aim to understand how the immune response is modulated in the presence of the stromal cell subpopulations. Based on our findings, we plan an evaluation of tumor sections to correlate the expression of markers that define the inhibitory stromal population with the prognosis of the tumor in patients with both breast and prostate cancer. Understanding the mechanism that underlies the suppression of cancer growth by stromal cells might open novel avenues in cancer therapy.
DFG Programme
Priority Programmes
