Carcinoembryonic antigen‐related cell adhesion molecule 1 negatively regulates granulocyte colony‐stimulating factor production by breast tumor‐associated macrophages that mediate tumor angiogenesis

Samineni, Sridhar; Zhang, Zhifang; Shively, John E.

doi:10.1002/ijc.28036

Cited by 16 publications

(15 citation statements)

References 47 publications

(111 reference statements)

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“…M1 macrophages appear to have a proangiogenic function early in tumorigenesis [ 33 ], when the tumor needs blood vessels formation to grow; this fact supports the idea of the role that M1 plays in the early stages of breast tumor formation and it seems to be one of the first immune cells present in the inflammatory process. But, in advanced breast cancers, macrophages resemble the M2 phenotype, while M1 phenotype has not been found; this is the reason why TAMs are generally related more to a M2 phenotype than M1.…”

Section: Discussionmentioning

confidence: 68%

Maslinic Acid Enhances Signals for the Recruitment of Macrophages and Their Differentiation to M1 State

Sánchez-Quesada

López-Biedma

Gaforio

2015

Evidence-Based Complementary and Alternative Medicine

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The inflammatory process is involved in the genesis and evolution of different diseases like obesity, cardiovascular disease, and cancer. Macrophages play a central role in inflammation. In addition, they can regulate some stages of cancer development. Macrophages can polarize into M1 or M2 functional phenotype depending on the cytokines present in the tissue microenvironment. On the other hand, triterpenes found in virgin olive oil are described to present different properties, such as antitumoral and anti-inflammatory activity. The present study was designed to elucidate if the four major triterpenes found in virgin olive oil (oleanolic acid, maslinic acid, uvaol, and erythrodiol) are able to enhance M1 macrophage response which represents an important defense mechanism against cancer. Our results indicated that maslinic acid modulated the inflammatory response by enhancing the production of IL-8, IL-1α, and IL-1β; it promoted M1 response through the synthesis of IFN-γ; and finally it did not modify significantly the levels of NFκβ or NO. Overall, our results showed that maslinic acid could prevent chronic inflammation, which represents a crucial step in the development of some cancers.

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Section: Discussionmentioning

confidence: 68%

Maslinic Acid Enhances Signals for the Recruitment of Macrophages and Their Differentiation to M1 State

Sánchez-Quesada

López-Biedma

Gaforio

2015

Evidence-Based Complementary and Alternative Medicine

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“…For IL-6 release analysis, cells were treated with 500ng/mL LPS over time in the figure and supernatants were collected and analyzed using cytometric bead array. The concentration of inflammatory cytokines was measured using cytometric bead array (CBA; BD Biosciences, USA) as described previously 74 .…”

Section: Flow Cytometry and Cell Sortingmentioning

confidence: 99%

CEACAM1 regulates the IL-6 mediated fever response to LPS through the RP105 receptor in murine monocytes

Zhang

Placa

Kujawski

et al. 2018

Preprint

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short title: CEACAM1 regulation of monocyte IL6 response to LPS ABSTRACT Systemic inflammation and the fever response to pathogens are coordinately regulated by IL-6 and IL-1β. We previously showed that CEACAM1 regulates the LPS driven expression of IL-1β in murine neutrophils through its ITIM receptor. We now show that the prompt secretion of IL-6 in response to LPS is regulated by CEACAM1 expression on bone marrow monocytes.Ceacam1 -/mice over-produce IL-6 in response to an i.p. LPS challenge, resulting in prolonged surface temperature depression and overt diarrhea compared to their wild type counterparts.Intraperitoneal injection of a 64 Cu-labeled LPS, PET imaging agent shows confined localization to the peritoneal cavity, and fluorescent labeled LPS is taken up by myeloid splenocytes and muscle endothelial cells. While bone marrow monocytes and their progenitors (CD11b + Ly6G -) express IL-6 in the early response (<2 hours) to LPS in vitro, these cells are not detected in the bone marrow after in vivo LPS treatment due to their rapid and complete mobilization to the periphery. Notably, tissue macrophages are not involved in the early IL-6 response to LPS. In contrast to human monocytes, TLR4 is not expressed on murine bone marrow monocytes.Instead, the alternative LPS receptor RP105 is expressed and recruits MD1, CD14, Src, VAV1 and β-actin in response to LPS to produce IL-6. CEACAM1 negatively regulates RP105 signaling in monocytes by recruitment of SHP-1, resulting in the sequestration of pVAV1 and βactin from RP105. This novel pathway and regulation of IL-6 producing by CEACAM1 defines a novel role for monocytes in the fever of mice to LPS. (250 words) AUTHOR SUMMARYFever is one of the most common signs of the immune response to pathogens. The fever response to LPS or endotoxin of gram-negative bacteria is mediated by the combined action of two cytokines, IL-1β and IL-6. Regulation of their production in response to LPS is an important area of investigation. While we previously showed that the regulation of IL-1β production in neutrophils is through the lymphocyte receptor CEACAM1, we were interested if a similar mechanism operated for IL-6. Using a mouse model in which the CEACAM1 gene was knocked out, we show that IL-6 is over-produced compared to normal mice, and that monocytes, rather than neutrophils were the principal IL-6 producing cells. Surprisingly, murine monocytes do not express TLR4, the most commonly studied receptor for LPS, but instead express the low affinity LPS receptor, RP105, a receptor common expressed on B-cells.Furthermore, we show that bone marrow monocytes are rapidly released into the blood and home to tissues throughout the body in response to LPS. These findings explain much of the confusion in the literature concerning the immediate source of IL-6 and the distinct differences between murine and human monocytes in their in responses to LPS. (word count 196)

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“…The lack of ceacaM1 expression in breast tumors promoted the secretion of high levels of G-cSF by TaMs, which in turn promoted tumor angiogenesis and initial tumor establishment. it has been suggested that G-cSF plays an important role in tumor promotion induced by ceacaM1 downregulation (50). Generally, as shown in Fig.…”

Section: Role Of Tumor Microenvironment In the Effect Of G-csf On Brementioning

confidence: 87%

“…Protease-activated receptor (Par) 2 stimulates G-cSF expression in breast cancer and Par2 gene knockdown or Par2 antagonist use can reduce G-cSF secretion (49). carcinoembryonic antigen-related cell adhesion molecule (ceacaM) 1 expression in breast cancer McF-7 cells inhibits G-cSF secretion by M1 macrophages (50). in addition, G-cSF is the main downstream mediator of the mammalian target of rapamycin (mTor) pathway during the induction of myeloid-derived suppressor cell (MdSc) formation in breast cancer and Welte et al (51), suggested that the regulation of G-cSF by mTor may occur at the transcriptional level.…”

Section: Regulation Of G-csf Gene Expressionmentioning

confidence: 99%

The role of granulocyte colony‑stimulating factor in breast cancer development: A review

Liu

Yan

et al. 2020

Mol Med Report

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Granulocyte-colony-stimulating factor (G-cSF) is a member of the hematopoietic growth factor family that primarily affects the neutrophil lineage. G-cSF serves as a powerful mobilizer of peripheral blood stem cells and recombinant human G-cSF (rhG-cSF) has been used to treat granulocytopenia and neutropenia after chemotherapy for cancer patients. However, recent studies have found that G-cSF plays an important role in cancer progression. G-cSF expression is increased in different types of cancer cells, such as lung cancer, gastric cancer, colorectal cancer, invasive bladder carcinoma, glioma and breast cancer. However, it is unclear whether treatment with G-cSF has an adverse effect. The current review provides an overview of G-cSF in malignant breast cancer development and the data presented in this review are expected to provide new ideas for cancer therapy. Contents 1. introduction 2. Structure of the G-cSF gene 3. regulation of G-cSF gene expression 4. The G-cSF receptor 5. G-cSF expression in breast cancer 6. direct effects of G-cSF on breast cancer 7. role of tumor microenvironment in the effect of G-cSF on breast cancer 8. conclusions

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Carcinoembryonic antigen‐related cell adhesion molecule 1 negatively regulates granulocyte colony‐stimulating factor production by breast tumor‐associated macrophages that mediate tumor angiogenesis

Cited by 16 publications

References 47 publications

Maslinic Acid Enhances Signals for the Recruitment of Macrophages and Their Differentiation to M1 State

Maslinic Acid Enhances Signals for the Recruitment of Macrophages and Their Differentiation to M1 State

CEACAM1 regulates the IL-6 mediated fever response to LPS through the RP105 receptor in murine monocytes

The role of granulocyte colony‑stimulating factor in breast cancer development: A review

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