The perivascular niche regulates breast tumor dormancy

  title={The perivascular niche regulates breast tumor dormancy},
  author={Cyrus M. Ghajar and H{\'e}ctor Peinado and Hidetoshi Mori and Irina Matei and Kimberley J. Evason and H{\'e}l{\`e}ne Brazier and Dena Almeida and Antonius A. Koller and Katherine A. Hajjar and Didier Y. R. Stainier and Emily I. Chen and David C. Lyden and Mina J. Bissell},
  journal={Nature cell biology},
  pages={807 - 817}
In a significant fraction of breast cancer patients, distant metastases emerge after years or even decades of latency. How disseminated tumour cells (DTCs) are kept dormant, and what wakes them up, are fundamental problems in tumour biology. To address these questions, we used metastasis assays in mice and showed that dormant DTCs reside on microvasculature of lung, bone marrow and brain. We then engineered organotypic microvascular niches to determine whether endothelial cells directly… 
A perivascular niche in the bone marrow hosts quiescent and proliferating tumorigenic colorectal cancer cells
An important role of the perivascular BM niche for CRC cell dissemination is indicated and dTCs can be a potential source for tumor relapse and tumor heterogeneity.
Astrocytic laminin-211 drives disseminated breast tumor cell dormancy in brain.
Using serial intravital imaging of dormant and metastatic triple-negative breast cancer lines, escape from the single-cell or micrometastatic state is identified as the rate-limiting step towards brain metastasis.
Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy.
The data identify the interplay between NK cells and aHSCs as a master switch of cancer dormancy, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing metastatic outgrowth.
Prostate Cancer Dormancy and Reactivation in Bone Marrow
Recent discoveries that have improved the understanding of dormancy signaling and the role of the TME in modulating the epigenetic reprogramming of DCCs are discussed.
Angiopoietin-2 promotes ER+ breast cancer cell survival in bone marrow niche
It is demonstrated that ANGPT2 signaling activated after estrogen depletion paradoxically triggers ER+ tumor cell awakening from dormancy in their BM niche, partly indirectly via endothelial Tie2 receptor and partly directly via tumor cell surface integrin &1.
Molecular Pathways: Niches in Metastatic Dormancy
T tumor dormancy from the perspective of the niche is discussed and potential therapeutic targets are considered to help guide innovation in the care of patients with advanced cancer.
In vitro Models of Breast Cancer Metastatic Dormancy
In vitro models designed to study metastatic dormancy of breast cancer cells (BCCs) are focused on and components of the metastatic microenvironment that have been shown to impact on the dormant phenotype are addressed.
Human bone perivascular niche-on-a-chip for studying metastatic colonization
It is proposed that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization and persists in a slow-proliferative state associated with increased drug resistance.
Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy
Evidence is provided that the microenvironment of DTCs protects them from chemotherapy, independent of cell cycle status, and that prefacing adjuvant therapy with integrin inhibitors is a viable clinical strategy to eradicate D TCs and prevent metastasis.
A possible IDO1- TSP1 role in breast cancer dormancy
The data presented here suggests that endothelial cells induce breast cancer dormancy and drug resistance via TSP1, and suggests that an IFNγ/IDO1 pathway might decrease T SP1 synthesis leading to cancer cell proliferation and angiogenesis.


VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche
A requirement for VEGFR1+ haematopoietic progenitor cells that express vascular endothelial growth factor receptor 1 (VEGFR1) home to tumour-specific pre-metastatic sites and form cellular clusters before the arrival of tumour cells is demonstrated.
Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy.
This study identified a possible contributor to tumor dormancy: solitary, dormant cells that persist in tissue that could contribute to tumor recurrence and would not be susceptible to current therapeutic strategies targeting proliferating cells.
Interactions between cancer stem cells and their niche govern metastatic colonization
It is suggested that the education of stromal cells by infiltrating tumour cells is an important step in metastatic colonization and that preventing de novo niche formation may be a novel strategy for the treatment of metastatic disease.
Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs
Findings link TNC to pathways that support the fitness of metastasis-initiating breast cancer cells and highlight the relevance of TNC as an extracellular matrix protein of stem cell niches of the metastatic niche.
Dormant cancer cells retrieved from metastasis-free organs regain tumorigenic and metastatic potency.
Evidence that malignant growth of disseminated cancer cells is suspended indefinitely by microenvironmental conditions in metastasis-free organs, although it is still active in others of the same host, shows that neoplastic progression can be arrested and has far-reaching biological and clinical implications.
Controversies in clinical cancer dormancy
  • J. Uhr, K. Pantel
  • Biology, Medicine
    Proceedings of the National Academy of Sciences
  • 2011
Clinical cancer dormancy is defined as an unusually long time between removal of the primary tumor and subsequent relapse in a patient who has been clinically disease-free. The condition is
Stromal Endothelial Cells Directly Influence Cancer Progression
Secretions from quiescent ECs muted the proliferative and invasive phenotype of lung and breast cancer cells in vitro and reduced cancer cell protumorigenic and proinflammatory signaling, suggesting that endothelial cells do not just hang around in the background providing support, but are active participants in and potential targets for regulating the tumor microenvironment.
Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET
The data show that exosome production, transfer and education of bone marrow cells supports tumor growth and metastasis, has prognostic value and offers promise for new therapeutic directions in the metastatic process.