Mast cells: the JEKYLL and HYDE of tumor growth

Theoharides, Theoharis C.; Conti, Pio

doi:10.1016/j.it.2004.02.013

Cited by 304 publications

(239 citation statements)

References 66 publications

Supporting

Mentioning

227

Contrasting

Unclassified

Order By: Relevance

“…Mouse mammary carcinomas of various etiologies, that I have studied, did not contain significant numbers of mast cells. Some reports describe mast cells in human cancers [59] but the illustrations show only modest numbers and this accords with my own surgical pathology clinical experience. There is no convincing evidence that this cell lineage is causally involved in the carcinogenic or metastatic processes.…”

Section: Inflammation and Cancersupporting

confidence: 74%

Clinical and Biological Implications of the Tumor Microenvironment

Tarin¹

2012

Cancer Microenvironment

View full text Add to dashboard Cite

In normal tissues and organs, the activities of the constituent cells are strictly restricted to the tasks assigned to them during development. In addition they (with the exception of leukocytes) remain inflexibly confined to their territorial domains by regulatory interactions with their neighbors. This creates specialized local micro-environments in which structure and function are orderly, stable and tightly controlled by feed-back loops, within interacting regulatory networks. This system has considerable ability to adapt to changing conditions. In contrast, the microenvironment in regions where tumors are forming and expanding is characterized by progressive loss of specialized or differentiated cellular functions, disorderly molecular signals, degeneration of microscopical organ structure. This, coupled with the traffic of cells into and out of the tumor, often culminating in local invasion and metastasis to other organs. The nature of these disturbed molecular and cellular interactions is, by definition, highly unstable and increasingly unpredictable as time passes. It also varies between different tumors, sometimes even leading to regression. However, systematic analysis of this dysfunction in the tumor microcosm, using multiple modern research techniques, has revealed that all actively growing primary and secondary neoplasms share an absolute dependency upon support from adjacent non-neoplastic cells of the host. This support, in turn, continuously depends upon dynamic interplay between tumor and host cell populations, via signaling molecules and surface receptors in the tumor microenvironment. Such interplay determines the fate of the growing neoplasm. Such information, described and evaluated in this article, provides important new insights into the etiology of carcinogenesis and how tumor growth, invasion and metastasis might be therapeutically arrested. The facts and concepts assembled below, regarding the cancer microenvironment, demonstrate how modern molecular findings reveal the impact of the wide range of cancer diseases upon the internal cellular, tissue and organ environments of the whole individual and how this applies to designing new work to improve human cancer diagnosis and treatment. The article discusses several specific types of experimentally-induced and clinically common cancers to derive principles useful for interpreting events in the tumor microenvironment, which apply to cancers in general and especially to human malignant disease.

show abstract

Section: Inflammation and Cancersupporting

confidence: 74%

Clinical and Biological Implications of the Tumor Microenvironment

Tarin¹

2012

Cancer Microenvironment

View full text Add to dashboard Cite

show abstract

“…7,8 Upon activation, they release a plethora of pro-tumorigenic mediators, such as IL-8, VEGF, matrix metalloproteinases and proteases. 7,9 Angiogenesis factors (e.g., IL-8) and growth factors (e.g., VEGF) facilitate tumor growth and angiogenesis. Matrix metalloproteinases (e.g., MMP-9) and proteases (tryptase and chymase) degrade components of the extracellular matrix (ECM) and thus favoring the implantation of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Blokhuis

Derks

et al. 2018

OncoImmunology

View full text Add to dashboard Cite

Chronic inflammation drives the development of colorectal cancer (CRC), where tumor-infiltrating immune cells interact with cancer cells in a dynamic crosstalk. Mast cells (MC), one of earliest recruited immune cells, accumulate in CRC tissues and their density is correlated with cancer progression. However, the exact contribution of MC in CRC and their interaction with colon cancer cells is poorly understood. Here, we investigated the impact of primary human MC and their mediators on colon cancer growth using 2D and 3D coculture models. Primary human MC were generated from peripheral CD34+ stem cells. Transwell chambers were used to analyze MC chemotaxis to colon cancer. Colon cancer cells HT29 and Caco2 differentially recruited MC by releasing CCL15 or SCF, respectively. Using BrdU proliferation assays, we demonstrated that MC can directly support colon cancer proliferation and this effect was mediated by their cellular crosstalk. 3D coculture models with cancer spheroids further confirmed the pro-tumor effect of MC on colon cancer growth, where direct cell-cell contact is dispensable and increased production of multiple soluble mediators was detected. Moreover, TLR2 stimulation of MC promoted stronger growth of colon cancer spheroids. By examining the transcriptome profile of colon cancer-cocultured MC versus control MC, we identified several MC marker genes, which were deregulated in expression. Our study provides an advanced in vitro model to investigate the role of human MC in cancer. Our data support the detrimental role of MC in CRC development and provide a molecular insight into the cellular crosstalk between MC and colon cancer cells.

show abstract

“…From this point of view, mast cells may also be important as they have been reported to produce MMP-9 (24), and mast cell chymase activates pro-MMP-9 (25). Mast cell release of MMP-9 and other lytic enzymes has been associated with tumor progression and aggressiveness (26).…”

Section: Discussionmentioning

confidence: 99%

Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease

Sfiridaki¹,

Miyakis²,

Tsirakis³

et al. 2005

Clinical Chemistry and Laboratory Medicine (CCLM)

View full text Add to dashboard Cite

M. (2005). Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease. Clinical Chemical Laboratory Medicine, 43 (9), 934-938.Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease AbstractMultiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption. Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78"91.27 vs. 59.25"33.09 ng/mL, p-0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p-0.001, p-0.03, p-0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p-0.0001, p-0.01, respectively). MMP-9 levels were lower in patients compared with controls (p-0.001), whereas IL-6 and bone resorption marker levels were higher in patients than in controls (p-0.001 in all cases). Significant correlation was found between infiltration, MMP-9, free urine pyd, free urine dpd and NTx for each stage of the disease (p-0.03, p-0.003, p-0.002, p-0.003 and p-0.001, respectively). Levels of MMP-9 and of IL-6 in multiple myeloma correlate well with bone turnover rate and may be useful in disease evaluation. 2005/166Article in press -uncorrected proof Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease AbstractMultiple myeloma is characterized by accelerated production of the proteolytic enzyme matrix metalloproteinase (MMP)-9. We hypothesized that myeloma-produced MMP-9 may influence the rate of bone turnover in a paracrine manner. Thus, we examined the correlations of MMP-9 levels, disease severity, and bone turnover rate as evaluated by markers of bone formation and resorption.Thirty-seven newly diagnosed multiple myeloma patients (nine of Durie-Salmon stage I, 12 of stage II and 16 of stage III) and 12 age-matched controls were studied. Serum MMP-9 levels were significantly higher at stage II compared to stage I (188.78"91.27 vs. 59.25"33.09 ng/mL, p-0.004). Additionally, free urine pyridinolines (F-Pyd), free urine deoxy-pyridinolines (F-Dpd) and urine N-telopeptide fragment (NTx) were elevated, their level correlating with disease stage (p-0.001, p-0.03, p-0.001, respectively), as were bone marrow infiltration and serum interleukin-6 (IL-6) levels (p-0.0001, p-0.01, res...

show abstract

Mast cells: the JEKYLL and HYDE of tumor growth

Cited by 304 publications

References 66 publications

Clinical and Biological Implications of the Tumor Microenvironment

Clinical and Biological Implications of the Tumor Microenvironment

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Systemic levels of interleukin-6 and matrix metalloproteinase-9 in patients with multiple myeloma may be useful as prognostic indexes of bone disease

Contact Info

Product

Resources

About