Suppression of murine mammary carcinoma metastasis by the murine ortholog of breast cancer metastasis suppressor 1 (Brms1)

Samant, Rajeev S.; Debies, Michael T.; Hurst, Douglas R.; Moore, Brandon C.; Shevde, Lalita A.; Welch, Danny R.

doi:10.1016/j.canlet.2005.04.032

Cited by 29 publications

(20 citation statements)

References 9 publications

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“…BRMS1 has previously been demonstrated to function as a metastasis suppressor gene in in vivo models of breast cancer [3,21,22], melanoma [7], and ovarian cancer [23]. In this study we have shown that BRMS1 acts as a metastasis suppressor in NSCLC in cell culture models of metastatic movement, and in flank xenograft models.…”

Section: Discussionsupporting

confidence: 55%

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis and correlates with improved patient survival in non-small cell lung cancer

Smith¹,

Liu²,

Siefert³

et al. 2009

Cancer Letters

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Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene in several solid tumors. The role of BRMS1 in non-small cell lung cancer (NSCLC) is not well established. To assess in vitro and in vivo metastatic behavior H1299 NSCLC cells stably expressing BRMS1 or a vector control were created. BRMS1 expression significantly decreases both migration and invasion of NSCLC cells in vitro. Importantly, in flank xenografts, BRMS1 suppresses the formation of pulmonary and hepatic metastases but does not significantly affect primary tumor growth. To evaluate whether BRMS1 is related to the progression of NSCLC, we examined BRMS1 expression in human NSCLC. Both BRMS1 mRNA and protein levels are diminished in NSCLC compared to adjacent non-cancerous lung. BRMS1 expression is also lower in squamous cell carcinoma compared to adenocarcinoma. Moreover, preservation of tumor BRMS1 expression is associated with improved patient survival. Thus, BRMS1 functions as a metastasis suppressor and may be a prognostic indicator for human NSCLC.

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Section: Discussionsupporting

confidence: 55%

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis and correlates with improved patient survival in non-small cell lung cancer

Smith¹,

Liu²,

Siefert³

et al. 2009

Cancer Letters

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“…Therefore, this strategy clearly deviates from the natural history of the disease, resulting in neoplastic tissues that, from our experience, do not resemble the human malignancy. Likewise, the 4T1 breast carcinoma mouse model is frequently implemented upon inoculation of a large number of 4T1 cancer cells in the mammary fat pad of mice, ranging from 1 x 10 4 to more than 1x10 6 cells [15, 19–25]. However, in the present work it has been demonstrated that the inoculation of such high cell densities compromised the development of an efficient and reproducible model of spontaneous metastases.…”

Section: Discussionmentioning

confidence: 80%

“…Moreover, 4T1 murine tumors represent a clinically relevant triple-negative breast cancer model [16–18], which, alongside the cancer cell invasion and metastization, is an important challenge due to its lack of responsiveness to endocrine therapy. However, 4T1 metastatic breast cancer model suffers from the liability of fast growing tumors enhanced by the frequent inoculation of a large number of cells, rendering a tumor microenvironment that does not recapitulate human breast tumors, early mice euthanasia [15, 19–25], along with a surprisingly low metastatic take rate.…”

Section: Introductionmentioning

confidence: 99%

Inoculated Cell Density as a Determinant Factor of the Growth Dynamics and Metastatic Efficiency of a Breast Cancer Murine Model

et al. 2016

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4T1 metastatic breast cancer model have been widely used to study stage IV human breast cancer. However, the frequent inoculation of a large number of cells, gives rise to fast growing tumors, as well as to a surprisingly low metastatic take rate. The present work aimed at establishing the conditions enabling high metastatic take rate of the triple-negative murine 4T1 syngeneic breast cancer model. An 87% 4T1 tumor incidence was observed when as few as 500 cancer cells were implanted. 4T1 cancer cells colonized primarily the lungs with 100% efficiency, and distant lesions were also commonly identified in the mesentery and pancreas. The drastic reduction of the number of inoculated cells resulted in increased tumor doubling times and decreased specific growth rates, following a Gompertzian tumor expansion. The established conditions for the 4T1 mouse model were further validated in a therapeutic study with peguilated liposomal doxorubicin, in clinical used in the setting of metastatic breast cancer. Inoculated cell density was proven to be a key methodological aspect towards the reproducible development of macrometastases in the 4T1 mouse model and a more reliable pre-clinical assessment of antimetastatic therapies.

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“…The breadth of BRMS1-induced cellular changes are, in part, explained by its role as a component of core mSin3a:histone deacetylase complexes and interaction with the retinoblastoma tumor suppressor [8][9][10]. Thus, BRMS1 is positioned within the cell to regulate expression of a plethora of genes, yet histone deacetylase inhibitors (and by inference, the acetylases and deacetylases themselves) regulate only approximately 2% of known genes [11].…”

Section: Introductionmentioning

confidence: 99%

Microarray analysis reveals potential mechanisms of BRMS1-mediated metastasis suppression

Champine

Michaelson

Weimer

et al. 2007

Clin Exp Metastasis

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We used Affymetrix oligonucleotide microarrays to compare gene expression profiles of the metastatic parental breast cancer cell line MDA-MB-435 (435) and the non-metastatic daughter cell line created by the stable expression of the BReast cancer Metastasis Suppressor 1 (BRMS1) gene in 435 cells, MDA-MB-435-BRMS1 (435/BRMS1). Analysis of microarray data provided insight into some of the potential mechanisms by which BRMS1 inhibits tumor formation at secondary sites. Furthermore, due to the importance of the microenvironment, we also examined gene expression under different growth conditions (i.e., plus or minus serum), however, expression of 565 genes was significantly (adjusted p-value <0.05) altered regardless of in vitro growth conditions. BRMS1 expression significantly increased multiple major histocompatability complex (MHC) genes and significantly decreased expression of several genes associated with protein localization and secretion. The pattern of gene expression associated with BRMS1 expression suggests that metastasis suppression may be mediated by enhanced immune recognition, altered transport, and/or secretion of metastasis-associated proteins.

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Suppression of murine mammary carcinoma metastasis by the murine ortholog of breast cancer metastasis suppressor 1 (Brms1)

Cited by 29 publications

References 9 publications

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis and correlates with improved patient survival in non-small cell lung cancer

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis and correlates with improved patient survival in non-small cell lung cancer

Inoculated Cell Density as a Determinant Factor of the Growth Dynamics and Metastatic Efficiency of a Breast Cancer Murine Model

Microarray analysis reveals potential mechanisms of BRMS1-mediated metastasis suppression

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