Pleural Mesothelioma Instigates Tumor-Associated Fibroblasts To Promote Progression via a Malignant Cytokine Network

Li, Qi; Wang, Wei; Yamada, Tadaaki; Matsumoto, Kunio; Sakai, Katsuya; Bando, Yoshimi; Uehara, Hisanori; Nishioka, Yasuhiko; Sone, Saburo; Iwakiri, Shotaro; Itoi, Kazumi; Utsugi, Teruhiro; Yasumoto, Keiichi; Yano, Seiji

doi:10.1016/j.ajpath.2011.05.060

Cited by 56 publications

(76 citation statements)

References 29 publications

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“…Normal mesothelial cells express PDGFR-α while mesothelioma tumors express both PDGF-AA and PDGF-BB ligands as well as PDGFR-α and PDGFR-β (86)(87)(88). While the staining pattern of PDGFR-β immunoreactivity in frozen sections of MPM are consistent with MPM tumor cell expression of PDGFR-β, the function of PDGFR-β within tumor cells, as opposed to the associated stroma, has not been well described.…”

Section: Pdgfr Inhibitorsmentioning

confidence: 57%

Novel systemic therapy against malignant pleural mesothelioma

Mancuso

Neal

2017

Transl. Lung Cancer Res.

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Malignant pleural mesothelioma is an aggressive tumor of the pleura with an overall poor prognosis. Even with surgical resection, for which only a subset of patients are eligible, long term disease free survival is rare. Standard first-line systemic treatment consists of a platinum analog, an anti-metabolite, and sometimes anti-angiogenic therapy, but there is currently no well-established standard therapy for refractory or relapsed disease. This review focuses on efforts to develop improved systemic therapy for the treatment of malignant pleural mesothelioma (MPM) including cytotoxic systemic therapy, a variety of tyrosine kinase inhibitors and their downstream effector pathways, pharmacologic targeting of the epigenome, novel approaches to target proteins expressed on mesothelioma cells (such as mesothelin), arginine depletion therapy, and the emerging role of immunotherapy. Overall, these studies demonstrate the challenges of improving systemic therapy for MPM and highlight the need to develop therapeutic strategies to control this disease.

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Section: Pdgfr Inhibitorsmentioning

confidence: 57%

Novel systemic therapy against malignant pleural mesothelioma

Mancuso

Neal

2017

Transl. Lung Cancer Res.

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“…MSTO-211H, NCI-H28, NCI-H226, NCI-H2052, NCI-H2373, NCI-H2452, and Chinese hamster ovary (CHO) were purchased from American Type Culture Collection (Rockville, MD). MPM cell lines are divided into three histological origins, an epithelioid type (ACC-MESO-1, ACC-MESO-4, Y-MESO-9, Y-MESO-12, NCI-H290, NCI-H513, NCI-H226, and NCI-H2452), a sarcomatoid type (NCI-H28, NCI-H2052, and NCI-H2373), and a biphasic type (Y-MESO-8A, Y-MESO-14, EHMES-1, and MSTO-211H) (37)(38)(39). These cells were cultured in RPMI 1640 medium supplemented with 10% FBS (CRPMI 1640; Life Technologies, Grand Island, NY), 100 U/ml penicillin, and 100 mg/ml streptomycin (Meiji Seika Kaisha, Tokyo, Japan).…”

Section: Cell Linesmentioning

confidence: 99%

A Novel Targeting Therapy of Malignant Mesothelioma Using Anti-Podoplanin Antibody

Abe

Morita

Kaneko

et al. 2013

The Journal of Immunology

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Podoplanin (Aggrus), which is a type I transmembrane sialomucin-like glycoprotein, is highly expressed in malignant pleural mesothelioma (MPM). We previously reported the generation of a rat anti-human podoplanin Ab, NZ-1, which inhibited podoplanin-induced platelet aggregation and hematogenous metastasis. In this study, we examined the antitumor effector functions of NZ-1 and NZ-8, a novel rat-human chimeric Ab generated from NZ-1 including Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity against MPM in vitro and in vivo. Immunostaining with NZ-1 showed the expression of podoplanin in 73% (11 out of 15) of MPM cell lines and 92% (33 out of 36) of malignant mesothelioma tissues. NZ-1 could induce potent ADCC against podoplanin-positive MPM cells mediated by rat NK (CD161a+) cells, but not murine splenocytes or human mononuclear cells. Treatment with NZ-1 significantly reduced the growth of s.c. established tumors of MPM cells (ACC-MESO-4 or podoplanin-transfected MSTO-211H) in SCID mice, only when NZ-1 was administered with rat NK cells. In in vivo imaging, NZ-1 efficiently accumulated to xenograft of MPM, and its accumulation continued for 3 wk after systemic administration. Furthermore, NZ-8 preferentially recognized podoplanin expressing in MPM, but not in normal tissues. NZ-8 could induce higher ADCC mediated by human NK cells and complement-dependent cytotoxicity as compared with NZ-1. Treatment with NZ-8 and human NK cells significantly inhibited the growth of MPM cells in vivo. These results strongly suggest that targeting therapy to podoplanin with therapeutic Abs (i.e., NZ-8) derived from NZ-1 might be useful as a novel immunotherapy against MPM.

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“…[21][22][23] Because fibroblast accumulation was not evident at 35 days, we examined the expression of these factors on and after 35 days. However, we failed to observe differences in HGF, bFGF, and EREG mRNA expression among WT, CCL3-, or CCR5-deficient mice on and after 35 days after DSS injection (Supporting Information Fig.…”

Section: Reduction In Aom/dss-induced Hb-egf Expression In Ccl3-or CCmentioning

confidence: 99%

Crucial involvement of the CCL3‐CCR5 axis‐mediated fibroblast accumulation in colitis‐associated carcinogenesis in mice

Sasaki

Baba

Shinagawa

et al. 2014

Intl Journal of Cancer

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Patients with inflammatory bowel diseases often develop colon carcinoma. Combined treatment of azoxymethane (AOM) and dextran sulfate sodium (DSS) recapitulates colitis‐associated cancer in mice. AOM/DSS‐induced tumor formation was reduced in CCL3‐ or its specific receptor, CCR5‐deficient mice despite the presence of a massive infiltration of inflammatory cells. However, AOM/DSS‐induced type I collagen‐positive fibroblast accumulation in the colon was reduced in CCL3‐ or CCR5‐deficient mice. This was associated with depressed expression of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF), which is expressed mainly by fibroblasts. Moreover in vitro, CCL3 induced fibroblasts to proliferate and to enhance HB‐EGF expression. Furthermore, CCR5 blockade reduced tumor formation together with reduced fibroblast accumulation and HB‐EGF expression, even when administered after the development of multiple colon tumors. Thus, CCL3‐CCR5‐mediated fibroblast accumulation may be required, in addition to leukocyte infiltration, to induce full‐blown colitis‐associated carcinogenesis. Our studies shed light on a therapeutic potential of CCR5 antagonist for patients with colitis‐associated cancer.

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Pleural Mesothelioma Instigates Tumor-Associated Fibroblasts To Promote Progression via a Malignant Cytokine Network

Cited by 56 publications

References 29 publications

Novel systemic therapy against malignant pleural mesothelioma

Novel systemic therapy against malignant pleural mesothelioma

A Novel Targeting Therapy of Malignant Mesothelioma Using Anti-Podoplanin Antibody

Crucial involvement of the CCL3‐CCR5 axis‐mediated fibroblast accumulation in colitis‐associated carcinogenesis in mice

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