Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma

Miselis, Nathan R.; Wu, Zhijin; Rooijen, Nico van; Kane, Agnes B.

doi:10.1158/1535-7163.mct-07-0579

Cited by 100 publications

(72 citation statements)

References 45 publications

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“…Peritoneal neoplasia can originate de novo from the peritoneal tissues as primary tumours 40,41 . However, in most cases, it is derived from the invasion of adjacent tumours or metastasis of remote tumours 42,43 .…”

Section: Discussionmentioning

confidence: 99%

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles

et al. 2012

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Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

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Section: Discussionmentioning

confidence: 99%

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles

et al. 2012

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“…These approaches resulted in a substantial decrease in macrophage infiltration into the tumour, which led to inhibition of tumour angiogenesis, tumour growth and metastasis in different animal models 33,[44][45][46][47] . Although these experiments have been crucial in demonstrating pro-tumorigenic functions for macrophages in tumours, there are undoubtedly heterogenous consequences from broadly depleting all macrophage populations.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Microenvironmental regulation of metastasis

2008

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Metastasis is a multistage process that requires cancer cells to escape from the primary tumour, survive in the circulation, seed at distant sites and grow. Each of these processes involves ratelimiting steps that are influenced by non-malignant cells of the tumour microenvironment. Many of these cells are derived from the bone marrow, particularly the myeloid lineage, and are recruited by cancer cells to enhance their survival, growth, invasion and dissemination. This Review describes experimental data demonstrating the role of the microenvironment in metastasis, identifies areas for future research and suggests possible new therapeutic avenues.A variety of stromal cells in the surrounding environment are recruited to tumours, and these not only enhance growth of the primary cancer but also facilitate its metastatic dissemination to distant organs. Cancer cells in an aggressive primary mass are adept at exploiting that particular tissue microenvironment; however, once they leave these favourable surroundings, they must possess traits that will allow them to survive in new environments. In order for a metastasis to occur, the intravasated cancer cell must survive in the circulation, arrive at the target organ (seeding), extravasate into the parenchyma and show persistent growth 1 . Each of these stages is inefficient and some are rate limiting 1,2 . For example, senescence or apoptosis of cancer cells at the stage of entry into the metastatic site prevents the spread of the majority of circulating cells [2][3][4] . Seeding can occur to multiple organs, but metastatic tumours may grow in only one or a few 5 . There is also increasing evidence that in some cases cancer cells can lie dormant for many years, and that seeding may occur several years before diagnosis of the primary tumour [6][7][8][9][10] . In another phenomenon, termed angiogenic dormancy, there is a balance of proliferation and apoptosis that results in micrometastases that do not progress further 11,12 . The microenvironment clearly suppresses NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the malignancy of these potentially metastatic cells 10 , and their re-activation to form a clinically relevant metastasis probably occurs through perturbations in the microenvironment. Nevertheless, despite this evidence for early seeding and dormancy, tumour size and grade are the main predictors of metastasis, and this has been reinforced in recent studies in mouse models 13 and by gene expression analysis that linked large tumour size with metastasis-enhancing gene signatures 14 . It has been hypothesized that this may be due to metastatic re-seeding to primary tumours 15 . If this is the case, nothing is currently known about the underlying mechanisms. Successful metastatic outgrowth thus depends on the cumulative ability of cancer cells to appropriate distinct microenvironments at each step in the metastatic cascade: the primary tumour, systemic circulation and the final metastatic site. In this Review we discuss instruct...

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“…Inhibition of macrophage infiltration in tumors may inhibit metastasis and progression of secondary tumors [5,6]. The clinical significance of macrophage infiltration in tumor stroma, however, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer

Shabo

Olsson

Elkarim

et al. 2014

Cancer Microenvironment

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The scavenger receptor, CD163, is a macrophagespecific marker. Recent studies have shown that CD163 expression in breast and rectal cancer cells is associated with poor prognosis. This study was conducted to evaluate the relationship between CD163 expression as a macrophage trait in cancer cells, and macrophage infiltration and its clinical significance in colorectal cancer. Immunostaining of CD163 and macrophage infiltration were evaluated in paraffinembedded specimens, earlier analyzed for CD31, D2-40 and S-phase fraction, from primary tumors and normal colorectal mucosa of 75 patients with colorectal carcinoma. The outcomes were analyzed in relation to clinical-pathological data. CD163 expression was positive in cancer cells in 20 % of colorectal cancer patients and was related to advanced tumor stages (P=0.008) and unfavorable prognosis (p=0.001). High macrophage infiltration was related to shorter survival and positive CD163 expression in tumor cells. The prognostic impact of macrophage infiltration was independent of tumor stage and CD163 expression in cancer cells (p=0.034). The expression of macrophage phenotype in colorectal cancer cells is associated with macrophage density in tumor stroma and lower survival rates. Macrophage infiltration has an independent prognostic impact on mortality in colorectal cancer. In accordance with previous experimental studies, these findings provide new insights into the role of macrophages in colorectal cancer.

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Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma

Cited by 100 publications

References 45 publications

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles

Microenvironmental regulation of metastasis

Macrophage Infiltration in Tumor Stroma is Related to Tumor Cell Expression of CD163 in Colorectal Cancer

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