Related Experiment Video
Updated: Jun 29, 2026
An In Vitro Dormancy Model of Estrogen-sensitive Breast Cancer in the Bone Marrow: A Tool for Molecular Mechanism Studies and Hypothesis Generation
Published on: June 30, 2015
The urokinase receptor (u-PAR)--a link between tumor cell dormancy and minimal residual disease in bone marrow?
Heike Allgayer1, Julio A Aguirre-Ghiso
1Department of Experimental Surgery and Molecular Oncology of Solid Tumors, Medical Faculty Mannheim, University of Heidelberg, and DKFZ German Cancer Research Center Heidelberg, Germany. heike.allgayer@chir.ma.uni-heidelberg.de
Abstract:
Minimal residual disease (MRD) is hypothesized to be the major cause of tumor recurrence and metastasis even years and decades after primary cancer diagnosis and curative solid tumor resection. In these patients disseminated tumor cells reflecting MRD can be detected in the bone marrow years after treatment. It is to be assumed that genetic determinants and a complex interplay between the disseminated tumor cells and their microenvironment in the bone marrow are responsible for tumor cell dormancy and the final reactivation towards metastasis. The urokinase receptor (u-PAR), a critical regulator of invasion, intravasation, and metastasis, is found to be a key player in regulating the shift between single cell tumor dormancy and proliferation. This has mainly been attributed to a regulation by u-PAR of integrins, and the ability of the latter to propagate signals from fibronectin through the EGF-receptor, ERK, and p38 signaling. Interestingly, u-PAR is found in disseminated tumor cells in the bone marrow of solid cancer patients, and is associated with the expansion of these cells and clinical prognosis. Here we summarize and discuss findings on disseminated tumor cells in the bone marrow, MRD and the role of u-PAR in tumor biology, especially focusing on its specific role in providing a switch between tumor cell proliferation and dormancy. Finally, we discuss the hypothesis that u-PAR might be an essential molecule in bone marrow disseminated tumor cells for long-term survival during dormancy, and/or reactivation of their proliferation years after primary treatment.
Insights
Minimal residual disease (MRD) drives tumor recurrence. The urokinase receptor (u-PAR) in bone marrow disseminated tumor cells may control dormancy and reactivation, impacting long-term cancer outcomes.
Area of Science:
- Oncology
- Cancer Biology
- Metastasis Research
Background:
- Minimal residual disease (MRD) is a significant factor in late tumor recurrence and metastasis after primary cancer treatment.
- Disseminated tumor cells (DTCs) in the bone marrow are a hallmark of MRD, persisting for years post-treatment.
- The bone marrow microenvironment and genetic factors influence DTC dormancy and subsequent reactivation.
Purpose of the Study:
- To review the role of DTCs in the bone marrow and their association with MRD.
- To elucidate the function of the urokinase receptor (u-PAR) in regulating DTC proliferation and dormancy.
- To discuss u-PAR's potential as a key molecule in DTC survival and reactivation.
Main Methods:
- Literature review and synthesis of existing research findings.
- Discussion of molecular mechanisms involving u-PAR, integrins, and signaling pathways (EGF-receptor, ERK, p38).
- Analysis of u-PAR expression in DTCs and its correlation with clinical prognosis.
Main Results:
- u-PAR is identified as a critical regulator of the switch between tumor cell dormancy and proliferation.
- u-PAR influences integrin signaling pathways, affecting cell invasion and metastasis.
- Elevated u-PAR in bone marrow DTCs is linked to tumor cell expansion and poorer clinical outcomes.
Conclusions:
- u-PAR plays a pivotal role in controlling the balance between tumor cell dormancy and proliferation in the bone marrow.
- u-PAR may be essential for the long-term survival of dormant DTCs and their eventual reactivation.
- Targeting u-PAR could offer novel therapeutic strategies for preventing late tumor recurrence and metastasis.
