The role of macrophages in bone metastasis

Vasiliadou, I.; Holen, Ingunn

doi:10.1016/j.jbo.2013.07.002

Cited by 26 publications

(21 citation statements)

References 74 publications

(122 reference statements)

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“…Unlike cancer cells, FR-β expression on stromal cells correlated positively with cancer stage and the closely related category of lymph node involvement ( p -values of 0.0212 and 0.0293, respectively), even though none of the groups were significantly different from one another (Figure 5B ). While the mechanistic underpinnings of this correlation still need to be explored, it has been established for some time that tumor-associated macrophages greatly increase the invasiveness and metastatic potential of tumors [ 33 , 34 , 35 ]. Because the tumor associated macrophages in this study were strongly FR-β positive, as reported previously for melanoma, pancreatic and head and neck cancers [ 9 , 10 , 23 ], the correlation with cancer stage and lymph node involvement suggests the intriguing possibility that FR-β might not only constitute a useful indicator of tumor metastatic potential, but may also serve as an attractive target for folate-mediated delivery of drugs for reprogramming the tumor's immune environment.…”

Section: Resultsmentioning

confidence: 99%

Assessment of folate receptor-β expression in human neoplastic tissues

et al. 2015

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Over-expression of folate receptor alpha on cancer cells has been frequently exploited for delivery of folate-targeted imaging and therapeutic agents to tumors. Because limited information exists on expression of the beta isoform of the folate receptor in human cancers (FR-β), we have evaluated the immunohistochemical staining pattern of FR-β in 992 tumor sections from 20 different human cancer types using a new anti-human FR-β monoclonal antibody. FR-β expression was shown to be more pronounced in cells within the stroma, primarily macrophages and macrophage-like cells than cancer cells in every cancer type studied. Moreover, FR-β expression in both cancer and stromal cells was found to be statistically more prominent in females than males. A significant positive correlation was also observed between FR-β expression on stromal cells and both the stage of the cancer and the presence of lymph node metastases. Based on these data we conclude FR-β may constitute a good target for specific delivery of therapeutic agents to activated macrophages and that accumulation of FR-β positive macrophages in the stroma could serve as a useful indicator of a tumor's metastatic potential.

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Section: Resultsmentioning

confidence: 99%

Assessment of folate receptor-β expression in human neoplastic tissues

et al. 2015

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“…First, TAMs contribute to angiogenesis [22], a process detailing the formation of new blood vessels from pre-existing blood vessels. For example, production of IL-1β by TAMs induces expression of HIF-1 by the tumour cells [27]. An increase in TAM numbers correlates with an increase in tumour angiogenesis.…”

Section: Role Of Inflammatory Cells In Oncogenesismentioning

confidence: 99%

“…An increase in TAM numbers correlates with an increase in tumour angiogenesis. Factors such as IL-10, PGE 2 (prostaglandin E 2 ), and TGFβ1 expressed by TAMs can contribute to decreased IL-12 expression, thereby suppressing both T-cell and NK (natural killer) cell proliferation and their associated cytotoxic effects [27]. For example, production of IL-1β by TAMs induces expression of HIF-1 by the tumour cells [27].…”

Section: Role Of Inflammatory Cells In Oncogenesismentioning

confidence: 99%

Analysis of the intricate relationship between chronic inflammation and cancer

Chai

Siveen

Shanmugam

et al. 2015

Biochemical Journal

175

124

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Deregulated inflammatory response plays a pivotal role in the initiation, development and progression of tumours. Potential molecular mechanism(s) that drive the establishment of an inflammatory-tumour microenvironment is not entirely understood owing to the complex cross-talk between pro-inflammatory and tumorigenic mediators such as cytokines, chemokines, oncogenes, enzymes, transcription factors and immune cells. These molecular mediators are critical linchpins between inflammation and cancer, and their activation and/or deactivation are influenced by both extrinsic (i.e. environmental and lifestyle) and intrinsic (i.e. hereditary) factors. At present, the research pertaining to inflammation-associated cancers is accumulating at an exponential rate. Interest stems from hope that new therapeutic strategies against molecular mediators can be identified to assist in cancer treatment and patient management. The present review outlines the various molecular and cellular inflammatory mediators responsible for tumour initiation, progression and development, and discusses the critical role of chronic inflammation in tumorigenesis.

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“…Classical activation of macrophages and development of classically activated macrophages from monocytes evoke increased pro-inflammatory cytokine secretion and this M1 activation can be facilitated by exposure of macrophages to LPS and IFN [103,104].…”

Section: Macrophage Modulatorsmentioning

confidence: 99%

“…Alternative activation of macrophages elicits anti-inflammatory responses from macrophages and this M2 activation is achieved by exposing macrophages to IL-4 or IL-13 [103,104] Apart from these stimuli, macrophage modulation can also be brought about by epigenetic modifications, which are discussed in the next section.…”

Section: Macrophage Modulatorsmentioning

confidence: 99%

The role of macrophages in early phases of type 2 diabetes mellitus

Gunaseelan¹

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Inflammatory response is a hallmark process of type 2 diabetes mellitus (T2DM) development and progression. In overt hyperglycaemia, low-grade inflammation of the pancreatic islets is known to cause β-cell dysfunction paving way for the pathogenesis of T2DM. Macrophages are vital elements of the immune system that play a major role in both innate and adaptive immune responses. Increased macrophage infiltration in islets of Langerhans has been documented in humans and rodents with T2DM, thus exposing the islets to a pro-inflammatory milieu and thereby contributing to the disease. Though the detrimental role of islet macrophages in overt T2DM has been widely studied, the role of macrophages in islet cell remodelling during the (very) early stage of pre-diabetes, i.e. the compensatory phase, is hardly known. Elucidating the role of macrophages, and more so islet resident macrophages, along with their contribution to islet remodelling in early stages of T2DM can offer a window of opportunity to delay the progression of the disease. We established an animal model of pre-diabetes by exposing mice to a very short term high-fat diet (HFD) and utilized different established macrophage markers, to understand the dynamics of islet macrophages during this phase of pre-diabetes. We found a significant increase in islet macrophage cells within HFD fed mice at 21-days when compared to mice treated with the iso-calorie low-fat diet (LFD). To further determine whether macrophages play a direct role in islet dysfunction during the initial compensatory phase, we used diphtheria toxin receptor (DTR) mice to deplete macrophages during HFD feeding. Our results suggest that presence of macrophages may be important to promote compensatory islet hyperplasia (growth of islet size) at a much earlier stage of mouse T2DM pathogenesis. vi As macrophages seem to play a dual role in the pathogenesis of diabetes, with early anti-inflammatory role predominating while the later phase is marked by proinflammation and islet destruction, it is important to understand which phenotype/ or subtype modulation of macrophages (from pro-inflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype) will keep islets healthy and functioning. To this end, a recent report showed that a small molecule drug, I-BET151, which is a bromodomain and extra-terminal (BET) protein inhibitor, can perform dual function i.e. to modulate macrophages to adopt an anti-inflammatory phenotype and also aid in pancreatic β-cell regeneration and was then subsequently found to be particularly effective against type 1 diabetes mellitus (T1DM) development in non-obese diabetic (NOD) mice. As I-BET151 is emerging as a potential drug for diabetes treatment, we studied the effect of this drug on macrophage reprogramming to M2-like phenotype and the effect of macrophage secreted factors on β-cell, in vitro. We found reduced gene expression of pro-inflammatory cytokines in macrophages treated with I-BET151. We also found that I-BET151 has a direct effect on β-cell gene expressio...

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The role of macrophages in bone metastasis

Cited by 26 publications

References 74 publications

Assessment of folate receptor-β expression in human neoplastic tissues

Assessment of folate receptor-β expression in human neoplastic tissues

Analysis of the intricate relationship between chronic inflammation and cancer

The role of macrophages in early phases of type 2 diabetes mellitus

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