Inhibitors for Metastasis Development

Lang, Kerstin; Drell, Theodore L.; Zaenker, Kurt S.; Entschladen, Frank

doi:10.2174/157489206775246511

Cited by 10 publications

(8 citation statements)

References 142 publications

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“…It seems worth of note in this context, that stress has an influence on the estrogen metabolism, too [34]. As high concentrations or prolonged exposure to estrogen are known risk factors for breast cancer [35], an impaired estrogen production due to chronic stress might under certain conditions have a cancer-protective function [36].…”

Section: Epidemiological Aspectsmentioning

confidence: 99%

Neoneurogenesis and the Neuro-Neoplastic Synapse

Palm

Entschladen²

2007

Progress in Experimental Tumor Research

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A tumor is not an isolated entity within an organism, but tissue that strongly interacts with its environment. This interaction is however not restricted to direct cell-to-cell interactions, but generally comprises the susceptibility of tumor cells for chemokines and cytokines, as well as neurotransmitters and hormones by the expression of the according receptors. These signal substances have influences on tumor cell functions such as proliferation and migration. The other way round, tumor cells themselves release a broad range of these signal substances, which influence the cells of the environment. One of the first and most important interactions in this respect is the angiogenesis, which was discovered about 30 years ago. Tumor cells release angiogenic factors, i.e. the vascular endothelial growth factor as well as angiogenic chemokines among others. These factors initiate the vascularization of the tumor. Recently, a similar process was found for the development of lymphatic vessels in tumors. We herein seize these observations and combine them with arguments provided in the previous chapter, which leads us to the hypothesis that tumor cells may also be able to stimulate their own innervation; a process that we have termed neoneurogenesis.

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Section: Epidemiological Aspectsmentioning

confidence: 99%

Neoneurogenesis and the Neuro-Neoplastic Synapse

Palm

Entschladen²

2007

Progress in Experimental Tumor Research

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“…Nonetheless, approximately 30% of treated BC patients develop distant metastases [5] and these significantly account for 90% of breast cancer deaths [6]. Consequently, therapeutic strategies are needed that target metastasis [7,8].…”

Section: Introductionmentioning

confidence: 99%

Beta-Blocker Drug Therapy Reduces Secondary Cancer Formation in Breast Cancer and Improves Cancer Specific Survival

et al. 2010

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AbstrAct:Laboratory models show that the beta-blocker, propranolol, can inhibit norepinephrine-induced breast cancer cell migration. We hypothesised that breast cancer patients receiving beta-blockers for hypertension would show reduced metastasis and improved clinical outcome. Three patient subgroups were identified from the medical records of 466 consecutive female patients (median age 57, range 28-71) with operable breast cancer and follow-up (>10 years). Two subgroups comprised 43 and 49 hypertensive patients treated with beta-blockers or other antihypertensives respectively, prior to cancer diagnosis. 374 patients formed a nonhypertensive control group. Metastasis development, disease free interval, tumour recurrence and hazards risk were statistically compared between groups. KaplanMeier plots were used to model survival and DM. Beta-blocker treated patients showed a significant reduction in metastasis development (p=0.026), tumour recurrence (p=0.001), and longer disease free interval (p=0.01). In addition, there was a 57% reduced risk of metastasis (Hazards ratio=0.430; 95% CI=0.200-0.926, p=0.031), and a 71% reduction in breast cancer mortality after 10 years (Hazards ratio=0.291; 95% CI=0.119-0.715, p=0.007). This proof-of-principle study showed beta-blocker therapy significantly reduces distant metastases, cancer recurrence, and cancer-specific mortality in breast cancer patients suggesting a novel role for beta-blocker therapy. A larger epidemiological study leading to randomised clinical trials is needed for breast and other cancer types including colon, prostate and ovary.

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“…Endocrine therapy has been shown to have a positive effect on the treatment of advanced metastatic disease (1, 2). Despite these positive effects, initial or acquired resistance to endocrine therapies frequently occurs with tumors recurring as metastasis, which is the leading cause of death from breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Significance of PELP1 in ER-Negative Breast Cancer Metastasis

Roy

Chakravarty

Cortez

et al. 2012

Molecular Cancer Research

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Breast cancer metastasis is a major clinical problem. The molecular basis of breast cancer progression to metastasis remains poorly understood. PELP1 is an estrogen receptor (ER) coregulator that has been implicated as a proto-oncogene whose expression is deregulated in metastatic breast tumors and whose expression is retained in ER-negative tumors. We examined the mechanism and significance of PELP1-mediated signaling in ER-negative breast cancer progression using two ER-negative model cells (MDA-MB231 and 4T1 cells) that stably express PELP1-shRNA. These model cells had reduced PELP1 expression (75% of endogenous levels) and exhibited less propensity to proliferate in growth assays in vitro. PELP1 down regulation substantially affected migration of ER-negative cells in Boyden chamber and invasion assays. Using mechanistic studies, we found that PELP1 modulated expression of several genes involved in the epithelial mesenchymal transition EMT including MMPs, Snail1, Twist, and ZEB. In addition, PELP1 knockdown reduced the in vivo metastatic potential of ER-negative breast cancer cells and significantly reduced lung metastatic nodules in a xenograft assay. These results implicate PELP1 as having a role in ER-negative breast cancer metastasis, reveal novel mechanism of coregulator regulation of metastasis via promoting cell motility / EMT by modulating expression of genes, and suggest PELP1 may be a potential therapeutic target for metastatic ER-negative breast cancer.

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Inhibitors for Metastasis Development

Cited by 10 publications

References 142 publications

Neoneurogenesis and the Neuro-Neoplastic Synapse

Neoneurogenesis and the Neuro-Neoplastic Synapse

Beta-Blocker Drug Therapy Reduces Secondary Cancer Formation in Breast Cancer and Improves Cancer Specific Survival

Significance of PELP1 in ER-Negative Breast Cancer Metastasis

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