The bone microenvironment increases phenotypic plasticity of ER+ breast cancer cells

Bado, Igor; Zhang, Weijie; Hu, Jingyuan; Xu, Zhan; Wang, Hai; Sarkar, Poonam; Li, Lucian; Wan, Ying-Wooi; Li, Jun; Wu, Wenyi; Lo, Hin Ching; Kim, Ik Sun; Singh, Swarnima; Janghorban, Mahnaz; Muscarella, Aaron M.; Goldstein, Amit; Singh, Purba; Jeong, Hyun-Hwan; Liu, Chaozhong; Schiff, Rachel; Huang, Shixia; Ellis, Matthew J.; Gaber, M. Waleed; Gugala, Zbigniew; Liu, Zhandong; Zhang, Xiang H.-F.

doi:10.1016/j.devcel.2021.03.008

Cited by 74 publications

(47 citation statements)

References 84 publications

(92 reference statements)

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“…The presence of cancer cells thereby results in a vicious cycle of osteoblast activity and osteoclastogenesis that feeds back and enhances tumor growth (Esposito et al , 2018 ). Notably, it has been shown recently that the bone microenvironment enhances phenotypic EZH2‐mediated plasticity of ER‐positive DTCs, which boosts further dissemination of cancer cells to other organs (Bado et al , 2021 ). The bone microenvironment can also enhance the metastatic spread in triple‐negative breast cancer models (Zhang et al , 2021b ).…”

Section: Interaction With Specialized Tissue‐resident Cellsmentioning

confidence: 99%

Feed‐forward loops between metastatic cancer cells and their microenvironment—the stage of escalation

2022

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Breast cancer is the most frequent cancer among women, and metastases in distant organs are the leading cause of the cancerrelated deaths. While survival of early-stage breast cancer patients has increased dramatically, the 5-year survival rate of metastatic patients has barely improved in the last 20 years. Metastases can arise up to decades after primary tumor resection, hinting at microenvironmental factors influencing the sudden outgrowth of disseminated tumor cells (DTCs). This review summarizes how the environment of the most common metastatic sites (lung, liver, bone, brain) is influenced by the primary tumor and by the varying dormancy of DTCs, with a special focus on how established metastases persist and grow in distant organs due to feed-forward loops (FFLs). We discuss in detail the importance of FFL of cancer cells with their microenvironment including the secretome, interaction with specialized tissue-specific cells, nutrients/metabolites, and that novel therapies should target not only the cancer cells but also the tumor microenvironment, which are thick as thieves.

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Section: Interaction With Specialized Tissue‐resident Cellsmentioning

confidence: 99%

Feed‐forward loops between metastatic cancer cells and their microenvironment—the stage of escalation

2022

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“…Our recent study suggested that tumor cells exhibit phenotypic reprogramming when inoculated in the bone microenvironment. Specifically, the expression level of HER2 protein of HER2-negative BCa cells, such as MCF-7, was significantly up-regulated in the early stage of bone metastasis (44). We therefore evaluated the therapeutic effects of Tras-ALN using BCa cells that are not HER2-positive but exhibit HER2 up-regulation specifically in bones.…”

Section: Enhanced Therapeutic Efficacy Of Tras-aln In An Her2-negativ...mentioning

confidence: 99%

Harnessing the power of antibodies to fight bone metastasis

Tian

et al. 2021

Sci. Adv.

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Antibody-based therapies have proved to be of great value in cancer treatment. Despite the clinical success of these biopharmaceuticals, reaching targets in the bone microenvironment has proved to be difficult due to the relatively low vascularization of bone tissue and the presence of physical barriers. Here, we have used an innovative bone-targeting (BonTarg) technology to generate a first-in-class bone-targeting antibody. Our strategy involves the use of pClick antibody conjugation technology to chemically couple the bone-targeting moiety bisphosphonate to therapeutic antibodies. Bisphosphonate modification of these antibodies results in the delivery of higher conjugate concentrations to the bone metastatic niche, relative to other tissues. In xenograft mice models, this strategy provides enhanced inhibition of bone metastases and multiorgan secondary metastases that arise from bone lesions. Specific delivery of therapeutic antibodies to the bone, therefore, represents a promising strategy for the treatment of bone metastatic cancers and other bone diseases.

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“…Given that ARID1A-deficient tumors are sensitive to both tumor immunotherapy and PARP inhibitors, the combination of EZH2 inhibitors with PARP inhibitors or tumor immunotherapy with ARID1A-deficient tumors may be potential treatment strategies (62,125,126). EZH2 expression levels or protein modifications are involved in breast cancer initiation (127)(128)(129), progression or metastasis (130)(131)(132)(133), breast cancer stem cell regulation (134), and drug resistance (135)(136)(137)(138)(139)(140)(141). The high expression level of EZH2 is also considered an indicator of aggressive breast cancer (128).…”

Section: Ezh2 Inhibitionmentioning

confidence: 99%

ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target

et al. 2021

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Distant metastasis is the principal cause of mortality for breast cancer patients. Targeting specific mutations that have been acquired during the evolution process of advanced breast cancer is a potential means of enhancing the clinical efficacy of treatment strategies. In metastatic breast cancer, ARID1A is the most prevalent mutation of the SWI/SNF complex, which regulates DNA repair, recombination, and gene transcription. The low expression of ARID1A is associated with poor disease-free survival and overall survival of patients with luminal A or HER2-rich breast cancer. In addition, ARID1A plays a prominent role in maintaining luminal characteristics and has an advantage for identifying responses to treatment, including endocrine therapies, HDAC inhibitors and CDK4/6 inhibitors. The therapeutic vulnerabilities initiated by ARID1A alterations encourage us to explore new approaches to cope with ARID1A mutant-related drug resistance or metastasis. In this review, we describe the mutation profiles of ARID1A in metastatic breast cancer and the structure and function of ARID1A and the SWI/SNF complex as well as discuss the potential mechanisms of ARID1A-mediated endocrine resistance and therapeutic potential.

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The bone microenvironment increases phenotypic plasticity of ER+ breast cancer cells

Cited by 74 publications

References 84 publications

Feed‐forward loops between metastatic cancer cells and their microenvironment—the stage of escalation

Feed‐forward loops between metastatic cancer cells and their microenvironment—the stage of escalation

Harnessing the power of antibodies to fight bone metastasis

ARID1A Mutation in Metastatic Breast Cancer: A Potential Therapeutic Target

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