The role of transforming growth factor-β in suppression of hepatic metastasis from colon cancer

Are, Chandrakanth; Simms, Neka; Rajupt, Ashwani; Brattain, Michael G.

doi:10.1111/j.1477-2574.2010.00219.x

Cited by 5 publications

(4 citation statements)

References 34 publications

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“…However, function of TGF-β in cancer depends on the stage and context of tumour. TGF-β shows anti-tumoural activity at early stages by inhibiting proliferation of tumour cells, whereas expression of TGF-β is suppressed or its signalling pathways are inactivated at later stages [ 51 , 58 , 59 ]. Thus, our result of reduced expression of TGF-β1 in DL mice suggests inflammatory tumour microenvironment owing to hepatic metastasis.…”

Section: Discussionmentioning

confidence: 99%

Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer

2015

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Inhibition of carcinogenesis may be a consequence of attenuation of oxidative stress via activation of antioxidant defence system, restoration and stabilization of tumour suppressor proteins along with modulation of inflammatory mediators. Previously we have delineated significant role of curcumin during its long term effect in regulation of glycolytic pathway and angiogenesis, which in turn results in prevention of cancer via modulation of stress activated genes. Present study was designed to investigate long term effect of curcumin in regulation of Nrf2 mediated phase-II antioxidant enzymes, tumour suppressor p53 and inflammation under oxidative tumour microenvironment in liver of T-cell lymphoma bearing mice. Inhibition of Nrf2 signalling observed during lymphoma progression, resulted in down regulation of phase II antioxidant enzymes, p53 as well as activation of inflammatory signals. Curcumin potentiated significant increase in Nrf2 activation. It restored activity of phase-II antioxidant enzymes like GST, GR, NQO1, and tumour suppressor p53 level. In addition, curcumin modulated inflammation via upregulation of TGF-β and reciprocal regulation of iNOS and COX2. The study suggests that during long term effect, curcumin leads to prevention of cancer by inducing phase-II antioxidant enzymes via activation of Nrf2 signalling, restoration of tumour suppressor p53 and modulation of inflammatory mediators like iNOS and COX2 in liver of lymphoma bearing mice.

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Section: Discussionmentioning

confidence: 99%

Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer

2015

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“…68 Moreover, canonical TGF-β signaling in tumor cells of CRC patients suppressed liver metastasis formation. 95,96 This suggests that TGF-β acts as a tumor suppressor in liver metastasis. In contrast, TGF-β might act as a promoter of liver metastasis as well, as high TGF-β signaling is correlated with poor prognosis.…”

Section: Tgf-β Signaling In Tumor Cells Can Increase Liver Metastasismentioning

confidence: 99%

TGF‐β signaling in liver metastasis

Marvin

Heijboer

Dijke

et al. 2020

Clinical & Translational Med

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The presence of liver metastases drastically worsens the prognosis of cancer patients. The liver is the second most prevalent metastatic site in cancer patients, but systemic therapeutic opportunities that target liver metastases are still limited. To aid the discovery of novel treatment options for metastatic liver disease, we provide insight into the cellular and molecular steps required for liver colonization. For successful colonization in the liver, adaptation of tumor cells and surrounding stroma is essential. This includes the formation of a pre-metastatic niche, the creation of a fibrotic and immune suppressive environment, angiogenesis, and adaptation of tumor cells. We illustrate that transforming growth factor β (TGF-β) is a central cytokine in all these processes. At last, we devise that future research should focus on TGF-β inhibitory strategies, especially in combination with immunotherapy. This promising systemic treatment strategy has potential to eliminate distant metastases as the efficacy of immunotherapy will be enhanced.

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“…the primary tumor, but its metastasis [2,3]. Based on the century-old 'soil and seeds' theory, the interaction between metastatic cells and the microenvironment in host organs is critical for the formation of lethal metastases with organ specificity [4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model

Liu

et al. 2016

The FEBS Journal

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Paclitaxel is the most commonly used chemotherapeutic agent in breast cancer treatment. In addition to its well-known cytotoxic effects, recent studies have shown that paclitaxel has tumor-supportive activities. Importantly, paclitaxel levels are not maintained at the effective concentration through one treatment cycle; rather, the concentration decreases during the cycle as a result of drug metabolism. Therefore, a comprehensive understanding of paclitaxel's effects requires insight into the dose-specific activities of paclitaxel and their influence on cancer cells and the host microenvironment. Here we report that a low dose of paclitaxel enhances metastasis of breast cancer cells to the liver in mouse models. We used microarray analysis to investigate gene expression patterns in invasive breast cancer cells treated with low or clinically relevant high doses of paclitaxel. We also investigated the effects of low doses of paclitaxel on cell migration, invasion and metastasis in vitro and in vivo. The results showed that low doses of paclitaxel promoted inflammation and initiated the epithelial-mesenchymal transition, which enhanced tumor cell migration and invasion in vitro. These effects could be reversed by inhibiting NF-jB. Furthermore, low doses of paclitaxel promoted liver metastasis in mouse xenografts, which correlated with changes in estrogen metabolism in the host liver. Collectively, these findings reveal the paradoxical and dosedependent effects of paclitaxel on breast cancer cell activity, and suggest that increased consideration be given to potential adverse effects associated with low concentrations of paclitaxel during treatment.

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The role of transforming growth factor-β in suppression of hepatic metastasis from colon cancer

Abstract: The results of our study demonstrate for the first time that TGF-beta displays selective metastasis suppressor activity. These abnormal pathways can serve as selective targets for future development of targeted therapies.

Cited by 5 publications

References 34 publications

Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer

Long Term Effect of Curcumin in Restoration of Tumour Suppressor p53 and Phase-II Antioxidant Enzymes via Activation of Nrf2 Signalling and Modulation of Inflammation in Prevention of Cancer

TGF‐β signaling in liver metastasis

Low doses of paclitaxel enhance liver metastasis of breast cancer cells in the mouse model

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