Breast Cancer Cell–Derived Soluble CD44 Promotes Tumor Progression by Triggering Macrophage IL1β Production

Jang, Ja Young; Kim, Do-Hee; Lim, Jae Min; Lee, Joon Won; Jeong, Su Jin; Kim, Kwang Pyo; Surh, Young‐Joon

doi:10.1158/0008-5472.can-19-2288

Cited by 68 publications

(48 citation statements)

References 53 publications

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“…This pathway plays a major role in tumor lymphangiogenesis, murine lymph node, and lung metastasis, while NLRP3 expression is correlated with human mammary carcinoma development [ 140 , 141 ]. Similarly, murine 4T1 breast cancer cells release soluble CD44, which in turn induces macrophage-mediated IL-1β production, leading to tumor growth and lung metastases [ 142 ]. Human lung cancer cells release microparticles that bind TLR3 to trigger NLRP3 inflammasome pathways in macrophages and IL-1β secretion.…”

Section: Pro-and Anti-tumor Effects Of Il-1βmentioning

confidence: 99%

Interleukin-1β and Cancer

Rébé

Ghiringhelli

2020

Cancers

193

110

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Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene is induced after “priming” of the cells and a second signal is required to allow IL-1β maturation by inflammasome-activated caspase-1. IL-1β is then released and leads to transcription of target genes through its ligation with IL-1R1 on target cells. IL-1β expression and maturation are guided by gene polymorphisms and by the cellular context. In cancer, IL-1β has pleiotropic effects on immune cells, angiogenesis, cancer cell proliferation, migration, and metastasis. Moreover, anti-cancer treatments are able to promote IL-1β production by cancer or immune cells, with opposite effects on cancer progression. This raises the question of whether or not to use IL-1β inhibitors in cancer treatment.

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Section: Pro-and Anti-tumor Effects Of Il-1βmentioning

confidence: 99%

Interleukin-1β and Cancer

Rébé

Ghiringhelli

2020

Cancers

193

110

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“…In addition, breast cancer patients show highly increased serum levels of IL-1β which is dependent on tumor stage 18,19 . This elevated expression of IL-1β is more likely to be associated with establishment of inflammatory tumor microenvironment and breast cancer progression 18,[20][21][22] . Further, significant correlation was noticed between IL-1β expression and subsequent development of metastasis 23,24 .…”

Section: Involvement Of the Inflammasomes And Their Effector Moleculementioning

confidence: 99%

Dynamic roles of inflammasomes in inflammatory tumor microenvironment

2021

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The inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysregulated expression/activation of inflammasomes is implicated in pathogenesis of diverse inflammatory disorders. Recent studies have demonstrated that inflammasomes play a vital role in regulating the development and progression of cancer. This review focuses on fate-determining roles of the inflammasomes and the principal downstream effector cytokine, IL-1β, in the tumor microenvironment.

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“…Salivary and plasmatic detection of sCD44 have been evaluated as potential diagnostic biomarkers for head and neck cancer, but the conclusions are inconsistent [27][28][29]. Finally, preclinical studies suggested that sCD44 may be secreted by tumor cells in triple negative breast cancer and could play a critical role in tumor growth [30]. As the indications for immunotherapies, particularly anti-PD1, are increasing, the need for a reliable biomarker predictive of response has become critical.…”

Section: Introductionmentioning

confidence: 99%

Predictive Value of Soluble PD-1, PD-L1, VEGFA, CD40 Ligand and CD44 for Nivolumab Therapy in Advanced Non-Small Cell Lung Cancer: A Case-Control Study

Meyo

Jouinot

Leprieur³

et al. 2020

Cancers

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A large interindividual variability has been observed in anti Programmed cell Death 1 (anti-PD1) therapies efficacy. The aim of this study is to assess the correlation of soluble PD-1 (sPD-1), soluble Programmed cell Death Ligand 1 (sPD-L1), Vascular Endothelial Growth Factor A (VEGFA), soluble CD40 ligand (sCD40L) and soluble CD44 (sCD44), with survival in nivolumab-treated metastatic non-small cell lung cancer (NSCLC) patients. Plasma biomarkers were assayed at baseline and after two cycles of nivolumab. A cut-off of positivity for sPD-1, sPD-L1 and sCD40L expressions was defined as a plasma level above the lower limit of quantification. Baseline sPD-1 and sPD-L1 levels were subsequently analyzed in a control group of EGFR-mutated (Epidermal Growth Factor Receptor) NSCLC patients. Association between survival and biomarkers was investigated using Cox proportional hazard regression model. Eighty-seven patients were included (51 nivolumab-treated patients, 36 in EGFR-mutated group). In nivolumab group, baseline sPD-1, sPD-L1 and sCD40L were positive for 15(29.4%), 27(52.9%) and 18(50%) patients, respectively. We defined a composite criteria (sCombo) corresponding to sPD-1 and/or sPD-L1 positivity for each patient. In nivolumab group, baseline sCombo positivity was associated with shorter median progression-free survival (PFS) (78 days 95%CI (55–109) vs. 658 days (222-not reached); HR: 4.12 (1.95–8.71), p = 0.0002) and OS (HR: 3.99(1.63–9.80), p = 0.003). In multivariate analysis, baseline sCombo independently correlated with PFS (HR: 2.66 (1.17–6.08), p = 0.02) but not OS. In EGFR-mutated group, all patients were baseline sCombo positive; therefore this factor was not associated with survival. After two cycles of nivolumab, an increased or stable sPD-1 level independently correlated with longer PFS (HR: 0.49, 95%CI (0.30–0.80), p = 0.004) and OS (HR: 0.39, 95%CI (0.21–0.71), p = 0.002). VEGFA, sCD40L and sCD44 did not correlate with survival. We propose a composite biomarker using sPD-1and sPDL-1 to predict nivolumab efficacy in NSCLC patients. A larger validation study is warranted.

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Breast Cancer Cell–Derived Soluble CD44 Promotes Tumor Progression by Triggering Macrophage IL1β Production

Cited by 68 publications

References 53 publications

Interleukin-1β and Cancer

Interleukin-1β and Cancer

Dynamic roles of inflammasomes in inflammatory tumor microenvironment

Predictive Value of Soluble PD-1, PD-L1, VEGFA, CD40 Ligand and CD44 for Nivolumab Therapy in Advanced Non-Small Cell Lung Cancer: A Case-Control Study

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