Distant metastasis in triple-negative breast cancer

Tseng, Ling‐Ming; Hsu, Nancy; Chen, S C; Lu, Yen‐Shen; Lin, Chunru; Chang, Dan; Li, H; Lin, Yiing; Chang, Haṡok; Chao, Ta‐Chung; Ouyang, Fusheng; Hou, Ming‐Feng

doi:10.4149/neo_2013_038

Cited by 95 publications

(79 citation statements)

References 16 publications

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“…In the context of breast cancer, we utilized our quantitative ECM proteomics to begin to address this hypothesis by elucidating tissue-specific differences as well as similarities between the primary and liver metastatic site in the nulliparous female adult rat. We focused on the liver, as one of three common sites of breast cancer metastasis (57–59), which confers the worst prognosis (60–62). The resulting proteomic data were grouped into 10 functional classifications of proteins including: basement membrane, ECM regulator, fibril-associated collagens with interrupted triple helices (FACIT) collagen, fibrillar collagen, matricellular, other ECM, secreted ECM, and structural ECM, using DAVID, as described in Figure 1 (55).…”

Section: Resultsmentioning

confidence: 99%

Quantitative extracellular matrix proteomics to study mammary and liver tissue microenvironments

Goddard

Hill

Barrett

et al. 2016

The International Journal of Biochemistry & Cell Biology

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Normal epithelium exists within a dynamic extracellular matrix (ECM) that is tuned to regulate tissue specific epithelial cell function. As such, ECM contributes to tissue homeostasis, differentiation, and disease, including cancer. Though it is now recognized that the functional unit of normal and transformed epithelium is the epithelial cell and its adjacent ECM, we lack a basic understanding of tissue-specific ECM composition and abundance, as well as how physiologic changes in ECM impact cancer risk and outcomes. While traditional proteomic techniques have advanced to robustly identify ECM proteins within tissues, methods to determine absolute abundance have lagged. Here, with a focus on tissues relevant to breast cancer, we utilize mass spectrometry methods optimized for absolute quantitative ECM analysis. Employing an extensive protein extraction and digestion method, combined with stable isotope labeled Quantitative conCATamer (QconCAT) peptides that serve as internal standards for absolute quantification of protein, we quantify 98 ECM, ECM-associated, and cellular proteins in a single analytical run. In rodent models, we applied this approach to the primary site of breast cancer, the normal mammary gland, as well as a common and particularly deadly site of breast cancer metastasis, the liver. We find that mammary gland and liver have distinct ECM abundance and relative composition. Further, we show mammary gland ECM abundance and relative compositions differ across the reproductive cycle, with the most dramatic changes occurring during the pro-tumorigenic window of weaning-induced involution. Combined, this work suggests ECM candidates for investigation of breast cancer progression and metastasis, particularly in postpartum breast cancers that are characterized by high metastatic rates. Finally, we suggest that with use of absolute quantitative ECM proteomics to characterize tissues of interest, it will be possible to reconstruct more relevant in vitro models to investigate tumor-ECM dynamics at higher resolution.

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Section: Resultsmentioning

confidence: 99%

Quantitative extracellular matrix proteomics to study mammary and liver tissue microenvironments

Goddard

Hill

Barrett

et al. 2016

The International Journal of Biochemistry & Cell Biology

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“…TNBC has a strong potential to metastasize, and the majority of patients succumb to the disease due to distant metastasis (26). Recently, EMT has become the focal point of research into the metastatic process (27,28).…”

Section: Discussionmentioning

confidence: 99%

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5

Yao

2018

Exp Ther Med

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Abstract. MicroRNA (miR)-146a-5p functions as a tumor suppressor in various types of cancer. However, the role of miR-146a-5p in the development of triple-negative breast cancer (TNBC) is unclear. The present study aimed to investigate the role of miR-146a-5p in TNBC. The expression level of miR-146a-5p in TNBC tissues and cell lines was initially detected using reverse transcription-quantitative polymerase chain reaction. To predict the target gene of miR-146a-5p, TargetScan software was used and a dual luciferase assay was performed to verify the prediction. Furthermore, in order to explore the role of miR-146a-5p in TNBC, miR-146a-5p was overexpressed in TNBC cells using miR-146a-5p mimics. An MTT assay was performed to detect cell proliferation, and a Transwell assay was conducted to determine cell migration and invasion. Furthermore, western blotting was performed to measure associated protein expression. It was revealed that miR-146a-5p was downregulated in TNBC tissues and cell lines. SOX5 was indicated to be a target gene of miR-146a-5p and was upregulated in TNBC cells. Additionally, miR-146a-5p could inhibit TNBC cell proliferation, migration and invasion, repress the expression of mesenchymal markers (N-cadherin, vimentin and fibronectin) and increase epithelial marker (E-cadherin) expression. Furthermore, SOX5 overexpression eliminated the effects of miR-146a-5p mimics on TNBC cells. In conclusion, the data of the present study indicated that miR-146a-5p inhibits the proliferation and metastasis of TNBC cells by regulating SOX5.

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“…Additionally, patients with distant metastatic disease have a significantly shorter survival time relative to the other breast cancer subtypes [4]. The most common ectopic sites for TNBC to metastasize are the lungs, the liver, bones and the brain [5] with a higher propensity of metastasis to the lungs [3, 6]. Currently there is an unmet and compelling need for novel approaches to treat patients with metastatic TNBC.…”

Section: Introductionmentioning

confidence: 99%

Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer

et al. 2017

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Magnetic hyperthermia as a treatment modality is acquiring increased recognition for loco-regional therapy of primary and metastatic lung malignancies by pulmonary delivery of magnetic nanoparticles (MNP). The unique characteristic of magnetic nanoparticles to induce localized hyperthermia in the presence of an alternating magnetic field (AMF) allows for preferential killing of cells at the tumor site. In this study we demonstrate the effect of hyperthermia induced by low and high dose of MNP under the influence of an AMF using 3D tumor tissue analogs (TTA) representing the micrometastatic, perfusion independent stage of triple negative breast cancer (TNBC) that infiltrates the lungs. While application of inhalable magnetic nanocomposite microparticles (MnMs) to the micrometastatic TNBC model comprised of TTA generated from cancer and stromal cells, showed no measureable adverse effects in the absence of AMF-exposure, magnetic hyperthermia generated under the influence of an AMF in TTA incubated in a high concentration of MNP (1 mg/ mL) caused significant increase in cellular death/ damage with mechanical disintegration and release of cell debris indicating the potential of these inhalable composites as a promising approach for thermal treatment of diseased lungs. The novelty and significance of this study lies in the development of methods to evaluate in vitro the application of inhalable composites containing MNPs in thermal therapy using a physiologically relevant metastatic TNBC model representative of the microenvironmental characteristics in secondary lung malignancies.

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Distant metastasis in triple-negative breast cancer

Cited by 95 publications

References 16 publications

Quantitative extracellular matrix proteomics to study mammary and liver tissue microenvironments

Quantitative extracellular matrix proteomics to study mammary and liver tissue microenvironments

Effect of miR-146a-5p on proliferation and metastasis of triple-negative breast cancer via regulation of SOX5

Toxicity evaluation of magnetic hyperthermia induced by remote actuation of magnetic nanoparticles in 3D micrometastasic tumor tissue analogs for triple negative breast cancer

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