TNF inhibitor suppresses bone metastasis in a breast cancer cell line

Hamaguchi, Tatsuya; Wakabayashi, Hiroki; Matsumine, Akihiko; Sudo, Akihiro; Uchida, Atsushi

doi:10.1016/j.bbrc.2011.03.051

Cited by 69 publications

(50 citation statements)

References 29 publications

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“…TNF-α regulates CXCR4 on ovarian cancer cells [14]. Our previous reports demonstrated that infliximab inhibited CXCR4 protein expression in MDA-231 breast cancer cells [20]. In the present study, treatment of 143B cells with infliximab inhibited CXCR4 protein expression as efficiently as infliximab treatment of MDA-231 cells.…”

Section: Discussionsupporting

confidence: 48%

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Anti-Tumor Necrosis Factor Therapy Inhibits Lung Metastasis in an Osteosarcoma Cell Line

et al. 2014

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Background: Osteosarcoma is the most common primary malignancy of bone, and patients often develop pulmonary metastases. In a previous study, tumor necrosis factor (TNF)-α treatment of human osteosarcoma cells increases their metastatic ability in an animal model. TNF-α can act as a tumor necrosis factor and also as a tumor-promoting factor. In the present study, the effect of a TNF-α inhibitor on osteosarcoma aggressiveness and pulmonary metastases was investigated in vitro and in vivo. Methods: The effect of infliximab, a TNF-α inhibitor, on a metastatic osteosarcoma 143B cell growth and motility was investigated in vitro. An orthotopic xenograft model of 143B cell growth and spontaneous metastasis in SCID mice was used to assess the in vivo effect of infliximab. Results: Infliximab greatly reduced cell motility and pulmonary metastases in 143B cells. The mechanism of pulmonary metastasis inhibition involved decreased expression of CXC chemokine receptor 4 (CXCR4), Rho (small GTPase protein), and its effector. Conclusions: These results suggest a novel role for TNF-α inhibition in the reduction or prevention of pulmonary metastases of osteosarcoma in this animal model. TNF-α inhibition may become a preventive therapeutic option for the pulmonary metastases of osteosarcoma. © 2014 S. Karger AG, Basel

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Section: Discussionsupporting

confidence: 48%

“…Infliximab reduces pancreatic ductal adenocarcinoma tumor growth and liver metastasis in mice [12]. In our previous report, infliximab significantly suppressed bone metastases in the mice injected with MDA-MB-231 into the left ventricles [20]. …”

Section: Discussionmentioning

confidence: 99%

Anti-Tumor Necrosis Factor Therapy Inhibits Lung Metastasis in an Osteosarcoma Cell Line

et al. 2014

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“…It is well known that sTNF-a is associated with tumor metastasis (3), as sTNF-a induces angiogenesis by promoting VEGF expression (31,32) and stimulates production of chemokines and adhesion molecules (33,34) that are involved in tumor metastasis. High serum concentration of TNF-a in patients with breast cancer correlates with invasive tumors (35).…”

Section: Discussionmentioning

confidence: 99%

“…High serum concentration of TNF-a in patients with breast cancer correlates with invasive tumors (35). Because the tmTNF-a mAb did not neutralize sTNF-a, its inhibition of tumor metastasis may be attributed to (i) interference with constitutive NF-kB activation, reducing activation of its targeted prometastatic genes such as MMP9 and VEGF (33); and (ii) removal of tumor cells with a high density of tmTNF-a by ADCC and CDC, as those tumor cells may have high metastatic and invasive potential (further validation is needed). In addition, the CD44 molecule plays an important role in distant malignant metastasis.…”

Section: Discussionmentioning

confidence: 99%

Targeting Transmembrane TNF-α Suppresses Breast Cancer Growth

Zhou

Niu

et al. 2013

Cancer Research

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TNF antagonists may offer therapeutic potential in solid tumors, but patients who have high serum levels of TNF-a fail to respond to infliximab, suggesting consumption of the circulating antibody and loss of transmembrane TNF-a (tmTNF-a) on tumors by ectodomain shedding. Addressing this possibility, we developed a monoclonal antibody (mAb) that binds both full-length tmTNF-a and its N-terminal truncated fragment on the membrane after tmTNF-a processing but does not cross-react with soluble TNF-a. We documented high levels of tmTNF-a expression in primary breast cancers, lower levels in atypical hyperplasia or hyperplasia, but undetectable levels in normal breast tissue, consistent with the notion that tmTNF-a is a potential therapeutic target. Evaluations in vitro and in vivo further supported this assertion. tmTNF-a mAb triggered antibodydependent cell-mediated cytotoxicity against tmTNF-a-expressing cells but not to tmTNF-a-negative cells. In tumor-bearing mice, tmTNF-a mAb delayed tumor growth, eliciting complete tumor regressions in some mice. Moreover, tmTNF-a mAb inhibited metastasis and expression of CD44v6, a prometastatic molecule. However, the antibody did not activate tmTNF-a-mediated reverse signaling, which facilitates tumor survival and resistance to apoptosis, but instead inhibited NF-kB activation and Bcl-2 expression by decreasing tmTNF-a-positive cells. Overall, our results established that tmTNF-a mAb exerts effective antitumor activities and offers a promising candidate to treat tmTNF-a-positive tumors, particularly in patients that are nonresponders to TNF antagonists. Cancer Res; 73(13); 4061-74. Ó2013 AACR.

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“…Knockdown of CXCR4 expression has been demonstrated to reduce proliferation and invasion of ovarian cancer cells [266], and metastasis in breast cancer cells [267] and prostate cancer cells [268]. AMD3100, an anti-CXCR4 inhibitor, has consistently inhibited CXCR4 signaling and migration in in vivo experiments in a variety of cell lines [269][270][271].…”

Section: Introductionmentioning

confidence: 99%

Structure-based design of inhibitors of CXCR4.

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TNF inhibitor suppresses bone metastasis in a breast cancer cell line

Cited by 69 publications

References 29 publications

Anti-Tumor Necrosis Factor Therapy Inhibits Lung Metastasis in an Osteosarcoma Cell Line

Anti-Tumor Necrosis Factor Therapy Inhibits Lung Metastasis in an Osteosarcoma Cell Line

Targeting Transmembrane TNF-α Suppresses Breast Cancer Growth

Structure-based design of inhibitors of CXCR4.

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