The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis

Romero-Moreno, Ricardo; Curtis, Kimberly J.; Coughlin, Thomas R.; Miranda-Vergara, Maria Cristina; Dutta, Soumya; Natarajan, Aishwarya; Facchine, Beth A.; Jackson, Kristen M.; Nystrom, Lukas M.; Li, Jun; Kaliney, William; Niebur, Glen L.; Littlepage, Laurie E.

doi:10.1038/s41467-019-12108-6

Cited by 112 publications

(85 citation statements)

References 73 publications

(81 reference statements)

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“…Second, the CXCL5-CXCR2 axis has also been associated with the process by which circulating tumour cells home to the bone 39 . In addition, a more recent study showed its importance in colonization during bone metastasis 84 . In line with these studies, we observed fewer cancer cells in the BM after inhibition of CXCR2 in both LD and JL conditions, and a lower degree of metastasis in JL condition (but not in the LD group), but it remains unclear which one of these mechanisms (or both) might be responsible.…”

Section: Discussionmentioning

confidence: 99%

Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice

et al. 2020

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Breast cancer is the most common type of cancer worldwide and one of the major causes of cancer death in women. Epidemiological studies have established a link between night-shift work and increased cancer risk, suggesting that circadian disruption may play a role in carcinogenesis. Here, we aim to shed light on the effect of chronic jetlag (JL) on mammary tumour development. To do this, we use a mouse model of spontaneous mammary tumourigenesis and subject it to chronic circadian disruption. We observe that circadian disruption significantly increases cancer-cell dissemination and lung metastasis. It also enhances the stemness and tumour-initiating potential of tumour cells and creates an immunosuppressive shift in the tumour microenvironment. Finally, our results suggest that the use of a CXCR2 inhibitor could correct the effect of JL on cancer-cell dissemination and metastasis. Altogether, our data provide a conceptual framework to better understand and manage the effects of chronic circadian disruption on breast cancer progression.

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Section: Discussionmentioning

confidence: 99%

Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice

et al. 2020

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“…It is additionally interesting to note that 14/18 of the upregulated protein-validated factors are associated with poor prognosis or invasion in breast cancers, when measured in serum or tissue; this suggests that cells which secrete these factors would have a negative impact on prognosis 39,48,57,58,64,[66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] . It is also of interest to note that in these studies 8/14 of these poorprognostic factors have been seen to derive predominantly from stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype

et al. 2020

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The tumour microenvironment plays a crucial role in the growth and progression of cancer, and the presence of tumour-associated macrophages (TAMs) is associated with poor prognosis. Recent studies have demonstrated that TAMs display transcriptomic, phenotypic, functional and geographical diversity. Here we show that a sialylated tumour-associated glycoform of the mucin MUC1, MUC1-ST, through the engagement of Siglec-9 can specifically and independently induce the differentiation of monocytes into TAMs with a unique phenotype that to the best of our knowledge has not previously been described. These TAMs can recruit and prolong the lifespan of neutrophils, inhibit the function of T cells, degrade basement membrane allowing for invasion, are inefficient at phagocytosis, and can induce plasma clotting. This macrophage phenotype is enriched in the stroma at the edge of breast cancer nests and their presence is associated with poor prognosis in breast cancer patients.

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“…So, together, these data could explain the difference in terms of results with our study. Finally, a third study from Romero-Moreno et al [26] used another Ab (ab14935) mainly to stain mouse tissue. They report also a staining of bone and marrow cells from a human femoral head, but the nature of the cells expressing CXCR2 was not precise.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of CXCR2 in Breast Cancer

Boissière

Jacot

Fraisse

et al. 2020

Cancers

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The tumor microenvironment appears essential in cancer progression and chemokines are mediators of the communication between cancer cells and stromal cells. We have previously shown that the ligands of the chemokine receptor CXCR2 were expressed at higher levels in triple-negative breast cancers (TNBC). Our hypothesis was that CXCR2 expression could also be altered in breast cancer. Here, we have analyzed the potential role of CXCR2 in breast cancer in a retrospective cohort of 105 breast cancer patients. Expression of CXCR2, CD11b (a marker of granulocytes) and CD66b (a marker of neutrophils) was analyzed by immunohistochemistry on tumor samples. We demonstrated that CXCR2 stained mainly stromal cells and in particular neutrophils. CXCR2, CD11b and CD66b expression were correlated with high grade breast cancers. Moreover, TNBC displayed a higher expression of CXCR2, CD11b and CD66b than hormone receptor positive or Her2 positive tumors. High levels of CXCR2 and CD11b, but not CD66b, were associated with a higher infiltration of T lymphocytes and B lymphocytes. We also observed a correlation between CXCR2 and AP-1 activity. In univariate analyses, CXCR2, but not CD11b or CD66b, was associated with a lower risk of relapse; CXCR2 remained significant in multivariate analysis. Our data suggest that CXCR2 is a stromal marker of TNBC. However, higher levels of CXCR2 predicted a lower risk of relapse.

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The CXCL5/CXCR2 axis is sufficient to promote breast cancer colonization during bone metastasis

Cited by 112 publications

References 73 publications

Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice

Chronic circadian disruption modulates breast cancer stemness and immune microenvironment to drive metastasis in mice

Cancer-associated hypersialylated MUC1 drives the differentiation of human monocytes into macrophages with a pathogenic phenotype

Prognostic Value of CXCR2 in Breast Cancer

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