Lymphatic Endothelial Markers and Tumor Lymphangiogenesis Assessment in Human Breast Cancer

Metastasis via lymphatic vessels or blood vessels is the leading cause of death for breast cancer, and lymphangiogenesis and angiogenesis are critical prerequisites for the tumor invasion–metastasis cascade. The research progress for tumor lymphangiogenesis has tended to lag behind that for angiogenesis due to the lack of specific markers. With the discovery of lymphatic endothelial cell (LEC) markers, growing evidence demonstrates that the LEC plays an active role in lymphatic formation and remodeling, tumor cell growth, invasion and intravasation, tumor–microenvironment remodeling, and antitumor immunity. However, some studies have drawn controversial conclusions due to the variation in the LEC markers and lymphangiogenesis assessments used. In this study, we review recent findings on tumor lymphangiogenesis, the most commonly used LEC markers, and parameters for lymphangiogenesis assessments, such as the lymphatic vessel density and lymphatic vessel invasion in human breast cancer. An in-depth understanding of tumor lymphangiogenesis and LEC markers can help to illustrate the mechanisms and distinct roles of lymphangiogenesis in breast cancer progression, which will help in exploring novel potential predictive biomarkers and therapeutic targets for breast cancer.

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A New Invasion and Metastasis Molecule, Tiaml and Its Interaction With the Cytoskeleton Are Involved in Human Breast Cancer Progression

10.21236/ada392244 ◽

2000 ◽

Author(s):

Lilly Y. Bourguignon

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Human Breast Cancer ◽

Breast Cancer Progression ◽

Human Breast ◽

Invasion And Metastasis

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Proteomic Portrait of Human Breast Cancer Progression Identifies Novel Prognostic Markers

Cancer Research ◽

10.1158/0008-5472.can-11-3711 ◽

2012 ◽

Vol 72 (9) ◽

pp. 2428-2439 ◽

Cited By ~ 88

Author(s):

Tamar Geiger ◽

Stephen F. Madden ◽

William M. Gallagher ◽

Juergen Cox ◽

Matthias Mann

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Human Breast Cancer ◽

Prognostic Markers ◽

Breast Cancer Progression ◽

Human Breast

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Visfatin Mediates Malignant Behaviors through Adipose-Derived Stem Cells Intermediary in Breast Cancer

Cancers ◽

10.3390/cancers12010029 ◽

2019 ◽

Vol 12 (1) ◽

pp. 29 ◽

Cited By ~ 3

Author(s):

Jyun-Yuan Huang ◽

Yen-Yun Wang ◽

Steven Lo ◽

Ling-Ming Tseng ◽

Dar-Ren Chen ◽

...

Keyword(s):

Breast Cancer ◽

Stem Cells ◽

Cancer Progression ◽

Human Breast Cancer ◽

Breast Cancer Progression ◽

Akt Pathway ◽

Adipose Derived Stem Cells ◽

Human Breast ◽

Akt Inhibitor ◽

Promoting Effect

Adipose-derived stem cells (ADSCs) have been implicated in tumor growth and metastasis in breast cancer. ADSCs exhibit tumor tropism, and are of increasing clinical relevance due to the autologous fat grafting for breast reconstruction. Although we have previously shown that a high level of the adipocytokine visfatin in human breast cancer tissues correlated with tumor progression mediated by cAbl and STAT3, the effects of visfatin in the tumor microenvironment are unclear. To understand how visfatin modulates breast cancer within the tumor-stromal environment, we examined determinants of breast cancer progression using a visfatin-primed ADSCs-tumor co-culture model. ADSCs were isolated from tumor-free adipose tissue adjacent to breast tumors. ADSCs were treated with or without visfatin for 48 h and then collected for co-culture with breast cancer cell line MDA-MB-231 for 72 h in a transwell system. We found that the MDA-MB-231 cells co-cultured with visfatin-treated ADSCs (vADSCs) had higher levels of cell viability, anchorage independent growth, migration, invasion, and tumorsphere formation than that co-cultured with untreated ADSCs (uADSCs). Growth differentiation factor 15 (GDF15) upregulation was found in the co-culture conditioned medium, with GDF15 neutralizing antibody blocking the promoting effect on MDA-MB-231 in co-culture. In addition, a GDF15-induced AKT pathway was found in MDA-MB-231 and treatment with PI3K/AKT inhibitor also reversed the promoting effect. In an orthotopic xenograft mouse model, MDA-MB-231 co-injected with vADSCs formed a larger tumor mass than with uADSCs. Positive correlations were noted between visfatin, GDF15, and phosphor-AKT expressions in human breast cancer specimens. In conclusion, visfatin activated GDF15-AKT pathway mediated via ADSCs to facilitate breast cancer progression.

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Downregulation of the Novel Candidate Tumor Suppressor Gene NCOR2/SMRT in Human Breast Cancer Progression.

10.1158/0008-5472.sabcs-09-3150 ◽

2009 ◽

Author(s):

J. Geradts ◽

R. Saxena ◽

J. Groth ◽

M. Desouki ◽

J. Burchette ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Cancer Progression ◽

Human Breast Cancer ◽

Suppressor Gene ◽

Breast Cancer Progression ◽

The Novel ◽

Human Breast ◽

Candidate Tumor Suppressor Gene

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RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer

Frontiers in Oncology ◽

10.3389/fonc.2020.613470 ◽

2020 ◽

Vol 10 ◽

Author(s):

Danping Wang ◽

Yifan Wang ◽

Xuebiao Wu ◽

Xiangxing Kong ◽

Jun Li ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Colony Formation ◽

Human Breast Cancer ◽

Epithelial Mesenchymal Transition ◽

Epigenetic Modification ◽

Dependent Manner ◽

Human Breast ◽

Mesenchymal Transition ◽

E Cadherin

BackgroundE-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeutic targets in breast cancer.Experimental designWe studied the association of RNF20 with Snail and G9a by co-immunoprecipitation. We employed quantitative real-time PCR, ChIP, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the repression of E-cadherin in human breast cancer. We used a proteogenomic dataset that contains 105 breast tumor samples to determine the clinical relevance of RNF20 by Kaplan-Meier analyses.ResultsIn this study, we identified that Snail interacted with RNF20, an E3 ubiquitin-protein ligase responsible for monoubiquitination of H2BK120, and G9a, a methyltransferase for H3K9me2. RNF20 expression led to the inhibition of E-cadherin expression in the human breast cancer cells. Mechanically, we showed that RNF20 and H3K9m2 were enriched on the promoter of E-cadherin and knockdown of Snail reduced the enrichment of RNF20, showing a Snail-dependent manner. RNF20 expression enhanced breast cancer cell migration, invasion, tumorsphere and colony formation. Clinically, patients with high RNF20 expression had shorter overall survival.ConclusionRNF20 expression contributes to EMT induction and breast cancer progression through Snail-mediated epigenetic suppression of E-cadherin expression, suggesting the importance of RNF20 in breast cancer.

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