Increased Blood Clotting, Microvascular Density, and Inflammation in Eotaxin-Secreting Tumors Implanted into Mice

Samoszuk, Michael; Deng, Tom; Hamamura, Mark J; Su, Min‐Ying; Asbrock, Nicholas; Nalcioğlu, Orhan

doi:10.1016/s0002-9440(10)63310-x

Cited by 14 publications

(10 citation statements)

References 26 publications

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“…In addition, this robust resident eosinophilia occurred even in the earliest palpable tumors. Significantly, the eosinophil tumor accumulation occurred without any additional immunomodulating events as the injected melanoma cells were not manipulated to express either a unique antigen (e.g., ovalbumin [34]) or an eosinophil agonist cytokine/chemokine [25,33,49]. Moreover, the recipient wild type mice were not allergen sensitized/challenged to manipulate peripheral eosinophil numbers or their state of activation [34].…”

Section: Discussionmentioning

confidence: 99%

“…Irrespective of these difficulties, tumors arise and grow despite the presence of an eosinophil infiltrate and correlations with tumor growth have tended not to be linear (e.g., [63] vs. [34] vs. [25]). Moreover, exceptions to the rule exist with apparent dissociations between the presence of eosinophils (and/or the lack thereof) and rates of tumor onset/growth (e.g., [64]).…”

Section: Discussionmentioning

confidence: 99%

“…Eosinophils have been recognized in cellular infiltrates of tumors even in early histological studies of human cancers ( [21][22][23][24][25]). Clinical observations have shown that the appearance of eosinophils in solid tumors is common and occurs in several tumor types, particularly those of epithelial origin (e.g., colon and breast tumors (reviewed in [21,26])).…”

Section: Introductionmentioning

confidence: 99%

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Pivotal Advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response

Cormier

Taranova

Bedient

et al. 2006

Journal of Leukocyte Biology

153

129

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Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals, however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4 + T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with Th2-dependent immune responses and that recruitment is a dynamic ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial restricted. More importantly, these data also show that the mechanism(s) that elicits this host response occurs independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pivotal Advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response

Cormier

Taranova

Bedient

et al. 2006

Journal of Leukocyte Biology

153

129

View full text Add to dashboard Cite

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“…However, the reverse has been documented in cervix, lung, and colon carcinomas (29)(30)(31) and it has been suggested that eosinophils may play a role in suppressing tumor growth (32). Eotaxin has also been shown to directly mediate angiogenesis of CCR3 + microvascular endothelial cells (33), and eotaxin-producing melanomas have increased microvascular density and extensive thrombosis within the blood vessels of the tumor in a murine model system (34). It was hypothesized that eotaxin-1, although potentially responsible for recruiting eosinophils to the site of tumor and increasing blood vessel formation, may cause extensive thrombosis through degranulation of eosinophils and other cells (35), which may prevent effective infiltration of tumor by other components of the cellular immune system, such as cytotoxic T cells.…”

Section: Discussionmentioning

confidence: 99%

Eotaxin-2 and Colorectal Cancer: A Potential Target for Immune Therapy

Cheadle

Riyad

Subar

et al. 2007

Clinical Cancer Research

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Purpose: To study the production of chemokines by colorectal hepatic metastases.Experimental Design: Biopsies of resected colorectal hepatic metastases and nonneoplastic adjacent liver tissue were screened for chemokines using protein arrays and results were confirmed by ELISA and immunohistochemistry. Results: Two chemokines, eotaxin-2 and MCP-1, were found at elevated levels within the tumor biopsy compared with adjacent liver. The relative increase in expression from tumor was much higher for eotaxin-2 than MCP-1, with 10 of 25 donors having a >100-fold increase in expression compared with 0 of 24 donors for MCP-1. In a parallel analysis, eotaxin-2 was also found at elevated levels in the tumor region of primary colorectal cancer biopsies. Immunohistochemical staining indicated that carcinoembryonic antigen^positive tumor cells stained strongly for eotaxin-2, implicating these cells as the predominant source of the chemokine. In vitro studies confirmed that several colorectal tumor lines produce eotaxin-2 and that secretion of this chemokine could be depressed by IFN-g and enhanced by the Th2-type cytokines interleukin-4 and interleukin-13. Jurkat T cells were engineered to express the receptor for eotaxin-2 (CCR3). These cells effectively migrated in response to eotaxin-2 protein, suggesting that immune cells gene modified to express a chemokine receptor may have improved abilities to home to tumor. Conclusions: Taken together, these observations confirm eotaxin-2 as a chemokine strongly associated with primary and metastatic tumors of colorectal origin. Furthermore, the importance of this result may be a useful tool in the development of targeted therapeutic approaches to colorectal tumors.Chemokines are small molecules that mediate the migration of lymphocytes and other immune cells around the body through binding of appropriate G protein -coupled receptors (1). To date, at least 50 human chemokines and 18 chemokine receptors have been described and it is the complex interplay and degeneracy of these receptors and ligands that form a network thought to control cellular migration patterns. It is becoming increasingly clear that the chemokine network plays an important role in cancer through its effect on the growth and metastasis of tumor cells as well as in manipulating host-tumor interactions (2). Examples include the chemokine receptor CXCR4, which has been identified on at least 23 different tumor cell types and has also been shown to play an important role in the migration of metastatic tumor cells in vitro (3 -6). In colorectal cancer, strong CXCR4 expression is significantly associated with increased stage, lymph node metastasis, and reduced 3-year survival (7,8). Furthermore, chemokines can also drive tumor cell proliferation as observed in glioblastoma cells, which expressed high levels of CXCR4 (9).Colorectal cancer is the third most common cancer in the United States with 50% to 60% of patients progressing to develop hepatic metastases (10). Despite this prevalence of clinical cases, rel...

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“…Eosinophils were recognised in cellular infiltrates of tumours even in early histological studies of human cancers (18) and in several animal tumour models (6). Clinical observations confirmed the appearance of eosinophils particularly those of epithelial origin (e.g.…”

Section: Introductionmentioning

confidence: 91%

Mast cells and eosinophils in rat mammary gland tumours induced by N-Nitroso-N-methylurea

Kissová

Ševčíková

Révajová

et al. 2015

Bulletin of the Veterinary Institute in Pulawy

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The aim of the study was to evaluate the distribution and number of mast cells and eosinophils in rat mammary gland tumours induced by N-Nitroso-N-methylurea. The highest density of mast cells was found in cystic papillary adenocarcinomas of grade II. Eosinophils were detected only in the cystic papillary adenocarcinoma of grades I and II, in non-invasive cribriform adenocarcinoma and comedo-type carcinoma. Mast cell populations were observed perivascularly in the tumour stroma, in the host tumour interface, as well as in necrotic areas of neoplasms. Mast cells were observed to be intact according to their morphological changes, collectively referred to as degranulation. The obtained results indicate that mast cells and eosinophils play an important role in tumour micro-environment formation. The increased density of these cells in experimentally-induced rat mammary gland tumours suggests a poor prognosis in these cancers. Our results also confirmed that rat mammary gland tumours are good models for the study of breast cancers.

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Increased Blood Clotting, Microvascular Density, and Inflammation in Eotaxin-Secreting Tumors Implanted into Mice

Cited by 14 publications

References 26 publications

Pivotal Advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response

Pivotal Advance: Eosinophil infiltration of solid tumors is an early and persistent inflammatory host response

Eotaxin-2 and Colorectal Cancer: A Potential Target for Immune Therapy

Mast cells and eosinophils in rat mammary gland tumours induced by N-Nitroso-N-methylurea

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