Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases

Muraoka, Rebecca S.; Dumont, Nancy; Ritter, Christoph A.; Dugger, Teresa C.; Brantley, Dana M.; Chen, Jin; Easterly, Evangeline; Roebuck, L. Renee; Ryan, Sarah; Gotwals, Philip J.; Koteliansky, Victor; Arteaga, Carlos L.

doi:10.1172/jci0215234

Cited by 426 publications

(129 citation statements)

References 34 publications

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“…These agents have been administered orally as a pain medication, alternative medicine, or a component of food, indicating their low toxicity. Some studies have provided evidence that the blockade of TGF-b action leads to the suppression of distant metastasis in animal models (Muraoka et al 2002, Yang et al 2002. However, since TGF-b acts as a tumor suppressor, it is still possible that the suppression of TGF-b action itself may promote secondary carcinogenesis (Akhurst 2002;Johnson and Newfeld 2002).…”

Section: Discussionmentioning

confidence: 99%

Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-? through Akt inhibition

Shigeoka

Igishi

Matsumoto

et al. 2004

Journal of Cancer Research and Clinical Oncology

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Cell migration is essential for invasive and metastatic phenotypes of cancer cells. Potential chemopreventive agents of cancer-sulindac sulfide, caffeic acid phenethyl ester (CAPE), curcumin, and (+)-catechin-have been reported to interfere with several types of intracellular signaling. In this study, we examined the effects of these agents on transforming growth factorb(TGF-b)-induced motility and Akt phosphorylation in A549 cells. Judged by gold particle phagokinesis assay, sulindac sulfide, CAPE, and curcumin suppressed the motility of A549 cells promoted by TGF-b. LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signaling, also suppressed TGF-b-induced motility and Akt phosphorylation. Sulindac sulfide and CAPE, but not curcumin, suppressed TGF-b-induced Akt phosphorylation. We conclude that sulindac sulfide and CAPE suppress the motility promoted by TGF-b in lung adenocarcinoma cells through the suppression of Akt. Our observations raise the possibility that these agents, except for (+)-catechin, can be applied not only as chemopreventive agents but also as anti-metastatic therapy.Keywords A549 AE Akt AE TGF-b AE Sulindac sulfide AE Caffeic acid phenethyl ester Abbreviations CAPE Caffeic acid phenethyl ester AE TGF-b Transforming growth factor-b AE FAK Focal adhesion kinase AE MMP-2 Matrix metalloproteinase-2

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Section: Discussionmentioning

confidence: 99%

Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-? through Akt inhibition

Shigeoka

Igishi

Matsumoto

et al. 2004

Journal of Cancer Research and Clinical Oncology

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“…This TβRIIFc has stable high affinity to TGF-β and inhibits tumor cell motility, intravasation and metastasis (Muraoka et al 2002). TβRIIFc also shows activity of inhibiting bone metastasis and osteolysis and thus may be an effective agent for the treatment of bone metastasis (Hu et al 2010).…”

Section: Soluble Tgf-β Receptorsmentioning

confidence: 99%

Transforming growth factor-β signaling in tumor initiation, progression and therapy in breast cancer: an update

Zhang

Cao

et al. 2011

Cell Tissue Res

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Transforming growth factor-β (TGF-β) is a ubiquitous cytokine playing an essential role in cell proliferation, differentiation, apoptosis, adhesion and invasion, as well as in cellular microenvironment. In malignant diseases, TGF-β signaling features a growth inhibitory effect at an early stage but aggressive oncogenic activity at the advanced malignant state. Here, we update the current understanding of TGF-β signaling in cancer development and progression with a focus on breast cancer. We also review the current approaches of TGF-β signaling-targeted therapeutics for human malignancies.

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“…MISCs to promote metastasis [18]. In contrast, blockade of TGFb signaling inhibits mammary tumor cell viability, migration, and metastases [19].…”

Section: Introductionmentioning

confidence: 99%

Role of CD200 expression in regulation of metastasis of EMT6 tumor cells in mice

Gorczynski

Clark

Erin

et al. 2010

Breast Cancer Res Treat

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Previous studies have confirmed that levels of CD200 expression on the cells of the transplantable EMT6 mouse breast cancer line are increased markedly during growth in immunocompetent mice, unlike the persistent low levels of expression observed in NOD-SCID.IL-2(γr-/-) mice or mice with generalized over-expression of a CD200 transgene (CD200(tg) mice). Faster tumor growth occurs in both of these latter mice, with decreased evidence for a host immune reaction in lymph nodes draining the tumor (DLN). We now report evidence for a role for CD200 expression (by the host and/or tumor cells) in increased seeding of tumor cells to DLN in immunocompromised (CD200(tg) or NOD-SCID.IL-2(γr-/-)) vs immunocompetent mice, by limiting dilution cloning of tumor cells from DLN (vs contralateral lymph nodes, CLN), using control and GFP-tagged EMT6 cells. Neutralization of expressed CD200 by anti-CD200mAbs decreased the tumor metastasis at the same time as increasing detection of cytotoxic anti-tumor immune cells in DLN. Infusion of either anti-CD4 to deplete T-effector cells, or anti-TGFβ antibody, increased metastasis to DLN, as did indeed the infusion of EMT6 cells selected for the loss of TGFβRII expression. It is concluded that the increased CD200 expression by breast cancer cells (and/or host tissue) may be an important variable involved in determining the risk of metastasis.

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Blockade of TGF-β inhibits mammary tumor cell viability, migration, and metastases

Cited by 426 publications

References 34 publications

Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-? through Akt inhibition

Sulindac sulfide and caffeic acid phenethyl ester suppress the motility of lung adenocarcinoma cells promoted by transforming growth factor-? through Akt inhibition

Transforming growth factor-β signaling in tumor initiation, progression and therapy in breast cancer: an update

Role of CD200 expression in regulation of metastasis of EMT6 tumor cells in mice

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