Adipocytes and Neutrophils Give a Helping Hand to Pancreatic Cancers

Bronte, Vincenzo

doi:10.1158/2159-8290.cd-16-0682

Cited by 6 publications

(6 citation statements)

References 11 publications

(9 reference statements)

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“…40,41,45 This systemic and local inflammatory milieu may be conducive to tumor initiation and/or promotion. 60,61 The inflammatory microenvironment also is thought to be the major mechanism, by which chronic pancreatitis leads to PDAC development. 62–65 Targeting pancreatic inflammation by inhibiting cyclooxygenase activity, using aspirin, or targeted blockade of inflammatory cytokines has been shown to attenuate cancer development and/or growth.…”

Section: Overview Of Mechanisms Underlying the Increased Risk Of Pdacmentioning

confidence: 99%

Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer

Eibl¹,

Cruz‐Monserrate²,

Korc³

et al. 2018

Journal of the Academy of Nutrition and Dietetics

103

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Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest types of cancer. The worldwide estimates of its incidence and mortality in the general population are eight cases per 100,000 person-years and seven deaths per 100,000 person-years, and they are significantly higher in the United States than in the rest of the world. The incidence of this disease in the United States is more than 50,000 new cases in 2017. Indeed, total deaths due to PDAC are projected to increase dramatically to become the second leading cause of cancer-related deaths before 2030. Considering the failure to date to efficiently treat existing PDAC, increased effort should be undertaken to prevent this disease. A better understanding of the risk factors leading to PDAC development is of utmost importance to identify and formulate preventive strategies. Large epidemiologic and cohort studies have identified risk factors for the development of PDAC, including obesity and type 2 diabetes mellitus. This review highlights the current knowledge of obesity and type 2 diabetes as risk factors for PDAC development and progression, their interplay and underlying mechanisms, and the relation to diet. Research gaps and opportunities to address this deadly disease are also outlined.

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Section: Overview Of Mechanisms Underlying the Increased Risk Of Pdacmentioning

confidence: 99%

Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer

Eibl¹,

Cruz‐Monserrate²,

Korc³

et al. 2018

Journal of the Academy of Nutrition and Dietetics

103

View full text Add to dashboard Cite

show abstract

“…38 In addition, neutrophils have potential relevance to tumor progression, because emerging evidence suggests that neutrophils are active factors in cancer progression 39 and in the suppression of the antitumor immune response. 40 Thus, it is conceivable that tumor-adipocyte crosstalk modifies the inflammatory status of the tumor microenvironment, inducing tumor progression. In support of this model, SAA1-overexpressing TNBCs experienced greater infiltration by neutrophils and other pro-tumor immune cells than SAA1-low tumors.…”

Section: Discussionmentioning

confidence: 99%

“…Neutrophil recruitment appears to be the primary event in the initiation of the inflammatory cascade in adipose tissue during metabolic disorders 37 and mediates the development of AT inflammation 38 . In addition, neutrophils have potential relevance to tumor progression, because emerging evidence suggests that neutrophils are active factors in cancer progression 39 and in the suppression of the antitumor immune response 40 . Thus, it is conceivable that tumor‐adipocyte crosstalk modifies the inflammatory status of the tumor microenvironment, inducing tumor progression.…”

Section: Discussionmentioning

confidence: 99%

SAA1‐dependent reprogramming of adipocytes by tumor cells is associated with triple negative breast cancer aggressiveness

Rybinska,

Mangano,

Romero‐Cordoba

et al. 2024

Intl Journal of Cancer

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Triple negative breast cancers (TNBC) are characterized by a poor prognosis and a lack of targeted treatments. Their progression depends on tumor cell intrinsic factors, the tumor microenvironment and host characteristics. Although adipocytes, the primary stromal cells of the breast, have been determined to be plastic in physiology and cancer, the tumor‐derived molecular mediators of tumor‐adipocyte crosstalk have not been identified yet. In this study, we report that the crosstalk between TNBC cells and adipocytes in vitro beyond adipocyte dedifferentiation, induces a unique transcriptional profile that is characterized by inflammation and pathways that are related to interaction with the tumor microenvironment. Accordingly, increased cancer stem‐like features and recruitment of pro‐tumorigenic immune cells are induced by this crosstalk through CXCL5 and IL‐8 production. We identified serum amyloid A1 (SAA1) as a regulator of the adipocyte reprogramming through CD36 and P2XR7 signaling. In human TNBC, SAA1 expression was associated with cancer‐associated adipocyte infiltration, inflammation, stimulated lipolysis, stem‐like properties, and a distinct tumor immune microenvironment. Our findings constitute evidence that the interaction between tumor cells and adipocytes through the release of SAA1 is relevant to the aggressiveness of TNBC.

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“…On the other hand, the TME can provide an immunosuppressive niche to negatively regulate immune effector cells and facilitate the malignant progression of cancer (Ho et al, 2020), and causes the resistance of PC against various treatments such as chemotherapy, targeted therapy, and immunotherapy (Balachandran et al, 2019). The major immunosuppressive cell types in the TME of pancreatic cancer are tumor-associated macrophages (TAMs), myeloidderived suppressor cells (MDSCs), regulatory T cells (Treg), TH17, and tolerogenic DCs (Bronte and Tortora, 2016;Zhu et al, 2017;Ligorio et al, 2019;Zhang et al, 2020). These immunosuppressive cells promote tumor progression through a variety of mechanisms, including the direct mediation, inhibition of tumor-killing immune cells, induction of angiogenesis and lymphoangiogenesis (Ho et al, 2020), and promotion of metastasis.…”

Section: Interplays Between Neurotransmitters and The Immune Cells In Pancreatic Tme Immune Cells In The Tme Of Pancreatic Cancermentioning

confidence: 99%

Shedding Light on the Role of Neurotransmitters in the Microenvironment of Pancreatic Cancer

Liang

Gan

et al. 2021

Front. Cell Dev. Biol.

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Pancreatic cancer (PC) is a highly lethal malignancy with a 5-year survival rate of less than 8%. The fate of PC is determined not only by the malignant behavior of the cancer cells, but also by the surrounding tumor microenvironment (TME), consisting of various cellular (cancer cells, immune cells, stromal cells, endothelial cells, and neurons) and non-cellular (cytokines, neurotransmitters, and extracellular matrix) components. The pancreatic TME has the unique characteristic of exhibiting increased neural density and altered microenvironmental concentration of neurotransmitters. The neurotransmitters, produced by both neuron and non-neuronal cells, can directly regulate the biological behavior of PC cells via binding to their corresponding receptors on tumor cells and activating the intracellular downstream signals. On the other hand, the neurotransmitters can also communicate with other cellular components such as the immune cells in the TME to promote cancer growth. In this review, we will summarize the pleiotropic effects of neurotransmitters on the initiation and progression of PC, and particularly discuss the emerging mechanisms of how neurotransmitters influence the innate and adaptive immune responses in the TME in an autocrine or paracrine manner. A better understanding of the interplay between neurotransmitters and the immune cells in the TME might facilitate the development of new effective therapies for PC.

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Adipocytes and Neutrophils Give a Helping Hand to Pancreatic Cancers

Cited by 6 publications

References 11 publications

Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer

Diabetes Mellitus and Obesity as Risk Factors for Pancreatic Cancer

SAA1‐dependent reprogramming of adipocytes by tumor cells is associated with triple negative breast cancer aggressiveness

Shedding Light on the Role of Neurotransmitters in the Microenvironment of Pancreatic Cancer

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