Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment

Tulotta, Claudia; Lefley, Diane V.; Freeman, Katy; Gregory, Walter M.; Hanby, Andrew M.; Heath, Paul R.; Nutter, Faith; Wilkinson, J. Mark; Spicer-Hadlington, Amy R.; Liu, Xinming; Bradbury, Steven M.J.; Hambley, Lisa; Cookson, Victoria; Allocca, Gloria; Julio, Marianna Kruithof de; Coleman, Robert E.; Brown, Janet; Holen, Ingunn; Ottewell, Penelope D.

doi:10.1158/1078-0432.ccr-18-2202

Cited by 128 publications

(136 citation statements)

References 34 publications

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“…In line with previous results, IL-1β, IL-10 and CCL5 were involved in multiple signaling pathways that affect the development and progression of tumors. IL-1β caused expansion of the bone metastatic niche and led to tumor proliferation in breast cancer (45). IL-10 and integrin pathways have been reported to be strongly associated with head and neck cancer progression (46).…”

Section: Discussionmentioning

confidence: 99%

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2019

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Cytokines play an important role in the development of tumors. The purpose of the present study was to evaluate the mechanisms and cytokine level changes after transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). The Short Time-series Expression Miner (STEM) program was utilized to cluster cytokine expression profiles from the day before TACE to day 21 post-TACE. Based on the identified significant signatures, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. Cytokines were serially monitored in 60 evaluable patients to identify the results of the STEM program. Examination of the significant signatures identified 6 significant time-varied expression patterns for 507 cytokines (profiles 16, 18, 28, 41, 42 and 43). GO analysis was enriched in 'cytokine receptor-binding' and 'cytokine receptor activity', and the identified signaling pathways included 'cytokine-cytokine receptor interaction' and the 'JAK-STAT signaling pathway'. Ciliary neurotrophic factor (CNTF) level was increased early after TACE, reaching a peak on day 7 before finally decreasing from day 14 onwards, and was significantly positively correlated with aminotransferase level. Serum levels of pre-TACE IL-10 predicted the local tumor response and overall survival (OS) of the patients, while serum levels of post-TACE IL-1β only indicated the local tumor response of the patient. Overall, the present study identified cytokine time-series expression profiles of patients with HCC undergoing TACE. Early phase increases in CNTF after TACE were associated with post-treatment hepatic injury. IL-1β may reflect an objective response after TACE, while IL-10 may represent a biomarker for OS and the objective response pre-TACE, which may help patients with HCC to benefit from TACE.

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Section: Discussionmentioning

confidence: 99%

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

et al. 2019

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“…Additionally, it was observed that in tumour-naïve mice, a single dose of IL-1β dual selective antagonist reduces osteoclast and osteoblast activity and IL-1β expression, also following continuous administration of IL-1β dual selective antagonist for more than 21 days [45]. Similarly, Tulotta et al [46] using patient samples with stage II/III breast cancer, humanized mouse models of spontaneous breast cancer bone metastasis, genetic manipulation of breast cancer cells (MDA-MB-231-IL-1B+, T47D-IL-1B+ and MCF7-IL-1B+) and in vitro models (co-culture between HS5 or OB1 cells and MDA-MB-231 or T47D cells) demonstrated that not only the IL-1R antagonist, anakinra, but also the anti that a IL-1β antibody, canakinumab, inhibited breast tumor growth and progression to bone metastasis. Additionally, the production of IL-1β by tumor cells promoted epithelial-mesenchymal transition, invasion, migration, and bone colonization.…”

Section: Il-1mentioning

confidence: 87%

“…Additionally, the production of IL-1β by tumor cells promoted epithelial-mesenchymal transition, invasion, migration, and bone colonization. Contact between tumor and osteoblasts or bone marrow cells increased IL-1β secretion from all three cell types [46].…”

Section: Il-1mentioning

confidence: 98%

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Salamanna

Borsari

Contartese

et al. 2019

Cancers

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Breast cancer cells produce stimulators of bone resorption known as interleukins (ILs). However, data on the functional roles of ILs in the homing of metastatic breast cancer to bone are still fragmented. A systematic search was carried out in three databases (PubMed, Scopus, Web of Science Core Collection) to identify preclinical reports, and in three clinical registers (ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, European Union (EU) Clinical Trials Register) to identify clinical trials, from 2008 to 2019. Sixty-seven preclinical studies and 11 clinical trials were recognized as eligible. Although preclinical studies identified specific key ILs which promote breast cancer bone metastases, which have pro-metastatic effects (e.g., IL-6, IL-8, IL-1β, IL-11), and whose inhibition also shows potential preclinical therapeutic effects, the clinical trials focused principally on ILs (IL-2 and IL-12), which have an anti-metastatic effect and a potential to generate a localized and systemic antitumor response. However, these clinical trials are yet to post any results or conclusions. This inconsistency indicates that further studies are necessary to further develop the understanding of cellular and molecular relations, as well as signaling pathways, both up-and downstream of ILs, which could represent a novel strategy to treat tumors that are resistant to standard care therapies for patients affected by breast cancer bone disease.An initial literature search found 905 references, of which 151 articles were recognized using the PubMed database, 481 articles were recognized using Scopus, and 273 articles were found in the Web of Science Core Collection. Subsequently, the resulting references were submitted to a public reference manager (Mendeley 1.17.11) to eliminate duplicate articles, obtaining 666 articles. From the 666 articles obtained, after exclusion, 116 full-text articles were evaluated, of which 67 met the inclusion criteria. The 560 studies excluded from this review were excluded because they were meeting reports, reviews, book chapters, and case reports, and/or because they reported IL roles in primary breast tumor, as well as in lung, liver, and pulmonary metastasis, leukemia, osteosarcoma, ovarian tumor, melanoma, prostate cancer, autoimmune arthritis related to breast cancer, and other pathological conditions; however, they did not reveal the favorable development of bone metastases from breast cancer. In addition, we excluded studies where IL profiling was derived from breast cancer metastatic patients that were not grouped/analyzed based on the site of metastasis, and where breast cancer bone metastases were evaluated, but no IL roles/functions were examined. Finally, we also eliminated studies where responses to specific therapy (not IL-based) for breast cancer bone metastasis were analyzed, studies that evaluated the contributions of the sensory signaling pathways to neuropathic pain induced by breast cancer bone metastases, and studies on chronic s...

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“…In a humanized model of spontaneous breast cancer metastasis to bone, production of IL-1β by cancer cells promotes EMT (altered E-Cadherin, N-Cadherin, and G-Catenin), invasion, migration, and bone colonization. Inhibitor of IL-1β, Anakinra or Canakinumab, reduces metastasis and the number of cancer cells shed into the circulation ( 72 ). Clinical data show that continuous inhibition of IL-1 activity inhibits breast cancer growth and bone metastasis ( 73 ).…”

Section: Bmas and Mechanisms Associated With Cancer Cells Migration Amentioning

confidence: 99%

“…However, metastatic cancer cell proliferation does not occur immediately with a specific temporal pattern because cancer cells seeding at distant bones may remain quiescent until stimulus signals from the bone marrow microenvironment drive cancer cells proliferation into overt metastases in the bone ( 27 ). It is found that activated osteoclasts and increased osteoclastic bone resorption accelerate the growth of DTCs into overt metastases ( 72 ). In addition, it is hypothesized that when metastatic tumor cells arrive in the bone, they may be stimulated to form overt metastasis through an expansion of the tumor associated vasculature ( 72 ).…”

Section: Bmas and Mechanisms Responsible For Macrometastasis And Outgmentioning

confidence: 99%

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

Liu

Zhao

2020

Front. Oncol.

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Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

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Endogenous Production of IL1B by Breast Cancer Cells Drives Metastasis and Colonization of the Bone Microenvironment

Abstract: This is a repository copy of Endogenous production of IL-1B by breast cancer cells drives metastasis and colonisation of the bone microenvironment.

Cited by 128 publications

References 34 publications

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

Time‑series clustering of cytokine expression after transarterial chemoembolization in patients with hepatocellular carcinoma

What Is the Role of Interleukins in Breast Cancer Bone Metastases? A Systematic Review of Preclinical and Clinical Evidence

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

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