The bone microenvironment invigorates metastatic seeds for further dissemination

Zhang, Weijie; Bado, Igor; Hu, Jingyuan; Wan, Ying; Wu, Ling; Wang, Hai; Gao, Yang; Jeong, Hyun-Hwan; Xu, Zhan; Hao, Xiaoxin; Lege, Bree M.; Al‐Ouran, Rami; Li, Lucian; Li, Jiasong; Yu, Liqun; Singh, Swarnima; Lo, Hin Ching; Niu, Muchun; Li, Jun; Jiang, Weiyu; Li, Yang; Wong, Stephen T.C.; Cheng, Chonghui; Liu, Zhandong; Zhang, Xiang H.-F.

doi:10.1016/j.cell.2021.03.011

Cited by 163 publications

(130 citation statements)

References 58 publications

Supporting

Mentioning

111

Contrasting

Order By: Relevance

“…Another cancer cell might follow a similar pathway, but instead colonizes a metastatic site and forms a metastatic nodule (pathway B). Cells within this nodule, such as from the bone marrow metastases [ 39 ] could additionally re-intravasate and re-seed back to the primary tumor, if still in place (pathway C). Finally, cells within this nodule could re-disseminate to tertiary metastatic sites (pathway D) ( Figure 2 A).…”

Section: Discussionmentioning

confidence: 99%

“…Cancer cells can leave the primary tumor and extravasate at the secondary site (e.g., lungs) where they form metastatic foci [ 4 , 5 ]. Pathway C. From a metastatic focus, cancer cells can also re-intravasate and re-seed back to the primary tumor (if still in place), or travel and seed tertiary metastatic sites, Pathway D [ 12 , 13 , 14 , 39 ], enhancing metastatic burden. ( B ) Schematic representation showing that cancer cell re-dissemination from metastatic foci drastically enhances metastatic burden, which may contribute to cancer patient mortality.…”

Section: Figurementioning

confidence: 99%

See 1 more Smart Citation

Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

Borriello

Condeelis

Entenberg

et al. 2021

JCM

View full text Add to dashboard Cite

Although metastatic disease is the primary cause of mortality in cancer patients, the mechanisms leading to overwhelming metastatic burden are still incompletely understood. Metastases are the endpoint of a series of multi-step events involving cancer cell intravasation, dissemination to distant organs, and outgrowth to metastatic colonies. Here we show, for the first-time, that breast cancer cells do not solely disseminate to distant organs from primary tumors and metastatic nodules in the lymph nodes, but also do so from lung metastases. Thus, our findings indicate that metastatic dissemination could continue even after the removal of the primary tumor. Provided that the re-disseminated cancer cells initiate growth upon arrival to distant sites, cancer cell re-dissemination from metastatic foci could be one of the crucial mechanisms leading to overt metastases and patient demise. Therefore, the development of new therapeutic strategies to block cancer cell re-dissemination would be crucial to improving survival of patients with metastatic disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

Borriello

Condeelis

Entenberg

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…In addition, immune mediators including chemokines, cytokines, and exosomes have shown great therapeutic and prognostic value in the bone metastases. Furthermore, the bone microenvironment can also influence the metastatic seeding into other distant organs triggered by epigenetic reprogramming ( 70 ). Despite deep insights into the immune landscape of bone metastasis, future studies are still needed to identify novel determinants and elucidate their immunological mechanisms, which will pave the way for immune-based therapy and improve clinical outcomes.…”

Section: Perspectivesmentioning

confidence: 99%

Immune Modulation of Metastatic Niche Formation in the Bone

Cheng

Wang

2021

Front. Immunol.

View full text Add to dashboard Cite

Bone metastasis is commonly seen in patients with breast cancer, prostate cancer and lung cancer. Tumor-intrinsic factors and the tumor microenvironment cooperate to affect the formation of bone metastatic niche. Within the bone microenvironment, immune cells have been regarded as a major contributor to metastatic progression. In this review, we describe the dynamic roles of immune cells in regulating metastatic homing, seeding, dormancy, and outgrowth in the bone. We also summarize the diverse functions of immune molecules including chemokines, cytokines, and exosomes in remodeling the bone metastatic niche. Furthermore, we discuss the therapeutic and prognostic potential of these cellular and molecular players in bone metastasis.

show abstract

“…In the majority of cases, metastasis is first detected in the bone tissue [9]. Moreover, it has been shown recently that the bone microenvironment prepares cancer cells to disseminate to other organs in a mouse model [10].…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic Response to Acidosis Reveals Its Contribution to Bone Metastasis in Breast Cancer Cells

Yamagata

Freire

Villarinho

et al. 2022

Cells

View full text Add to dashboard Cite

Bone is the most common site of metastasis in breast cancer. Metastasis is promoted by acidosis, which is associated with osteoporosis. To investigate how acidosis could promote bone metastasis, we compared differentially expressed genes (DEGs) in MDA-MB-231 cancer cells in acidosis, bone metastasis, and bone metastatic tumors. The DEGs were identified using Biojupies and GEO2R. The expression profiles were assessed with Morpheus. The overlapping DEGs between acidosis and bone metastasis were compared to the bulk of the DEGs in terms of the most important genes and enriched terms using CytoHubba and STRING. The expression of the genes in this overlap filtered by secreted proteins was assessed in the osteoporosis secretome. The analysis revealed that acidosis-associated transcriptomic changes were more similar to bone metastasis than bone metastatic tumors. Extracellular matrix (ECM) organization would be the main biological process shared between acidosis and bone metastasis. The secretome genes upregulated in acidosis, bone metastasis, and osteoporosis-associated mesenchymal stem cells are enriched for ECM organization and angiogenesis. Therefore, acidosis may be more important in the metastatic niche than in the primary tumor. Acidosis may contribute to bone metastasis by promoting ECM organization. Untreated osteoporosis could favor bone metastasis through the increased secretion of ECM organization proteins.

show abstract

The bone microenvironment invigorates metastatic seeds for further dissemination

Cited by 163 publications

References 58 publications

Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

Breast Cancer Cell Re-Dissemination from Lung Metastases—A Mechanism for Enhancing Metastatic Burden

Immune Modulation of Metastatic Niche Formation in the Bone

Transcriptomic Response to Acidosis Reveals Its Contribution to Bone Metastasis in Breast Cancer Cells

Contact Info

Product

Resources

About