Contribution of CXCL12 secretion to invasion of breast cancer cells

Background: The winning model of the Sage Bionetworks/DREAM Breast Cancer Prognosis Challenge made use of several molecular features, called attractor metagenes, as well as another metagene defined by the average expression level of the two genes FGD3 and SUSD3. This is a follow-up study toward developing a breast cancer prognostic test derived from and improving upon that model.Methods: We designed a feature selector facility calculating the prognostic scores of combinations of features, including those that we had used earlier, as well as those used in existing breast cancer biomarker assays, identifying the optimal selection of features for the test.Results: The resulting test, called BCAM (Breast Cancer Attractor Metagenes), is universally applicable to all clinical subtypes and stages of breast cancer and does not make any use of breast cancer molecular subtype or hormonal status information, none of which provided additional prognostic value. BCAM is composed of several molecular features: the breast cancer-specific FGD3-SUSD3 metagene, four attractor metagenes present in multiple cancer types (CIN, MES, LYM, and END), three additional individual genes (CD68, DNAJB9, and CXCL12), tumor size, and the number of positive lymph nodes.Conclusions: Our analysis leads to the unexpected and remarkable suggestion that ER, PR, and HER2 status, or molecular subtype classification, do not provide additional prognostic value when the values of the FGD3-SUSD3 and attractor metagenes are taken into consideration.Impact: Our results suggest that BCAM's prognostic predictions show potential to outperform those resulting from existing breast cancer biomarker assays. Cancer Epidemiol Biomarkers Prev; 23(12); 2850-6. Ó2014 AACR.

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“…The other gene, CXCL12, is selected at N ¼ 7. Both of these genes are known to play important roles in cancer (19,20).…”

Section: Feature Selectionmentioning

confidence: 99%

Breast Cancer Prognostic Biomarker Using Attractor Metagenes and the FGD3–SUSD3 Metagene

Yang

Cheng

Tian

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…In addition, overexpression of SDF-1 can recruit more macrophages. The increased recruitment of cancerassociated macrophages (CAMs) is not contributed only to tumor angiogenesis by releasing vascular endothelial growth factor (VEGF) but also capable of inducing tumor cell motility and invasion through paracrine loop signaling (25)(26)(27)(28). On the contrary, hypoxia has been reported as an important driving force for the multistep process of metastasis, and the accumulated CAMs could exacerbate the oxidant microenvironment Representative blots are all presented and corresponding gray scale analysis is shown as mean ± SD of three independent experiments.…”

Section: Nf-κb Pathway Is Involved In Sdf-1-mediated Emt In Mcf-7 Cellsmentioning

confidence: 99%

Overexpression of SDF-1 activates the NF-κB pathway to induce epithelial to mesenchymal transition and cancer stem cell-like phenotypes of breast cancer cells

Kong

Guo

Liu

et al. 2016

International Journal of Oncology

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Abstract. The formation of EMT and EMT-induced CSC-like phenotype is crucial for the metastasis of tumor cells. The stromal cell-derived factor-1 (SDF-1) is upregulated in various human carcinomas, which is closely associated with proliferation, migration, invasion and prognosis of malignancies. However, limited attention has been directed towards the effect of SDF-1 on epithelial to mesenchymal transition (EMT) or cancer stem cell (CSC)-like phenotype formation in breast cancer cells and the related mechanism. In the present study, we screened MCF-7 cells with low SDF-1 expression level for the purpose of evaluating whether SDF-1 is involved in EMT and CSC-like phenotype formation in MCF-7 cells. The pEGFP-N1-SDF-1 plasmid was transfected into MCF-7 cells, and the stably overexpressed SDF-1 in MCF-7 cells was confirmed by real-time PCR and western blot analysis. Colony formation assay, MTT, wound healing assay and Transwell invasion assay demonstrated that overexpression of SDF-1 significantly boosted the proliferation, migration and invasion of MCF-7 cells compared with parental (P<0.05). Flow cytometry analysis revealed a notable increase of CD44 + / CD24 -subpopulation in SDF-1 overexpressing MCF-7 cells (P<0.001), accompanied by the apparently elevated ALDH activity and the upregulation of the stem cell markers OCT-4, Nanog, and SOX2 compared with parental (P<0.01).Besides, western blot analysis and immunofluorescence assay observed the significant decreased expression of E-cadherin and enhanced expression of slug, fibronectin and vimentin in SDF-1 overexpressed MCF-7 cells in comparison with parental (P<0.01). Further study found that overexpression of SDF-1 induced the activation of NF-κB pathway in MCF-7 cells. Conversely, suppressing or silencing p65 expression by antagonist or RNA interference could remarkably increase the expression of E-cadherin in SDF-1 overexpressed MCF-7 cells (P<0.001). Overall, the above results indicated that overexpression of SDF-1 enhanced EMT by activating the NF-κB pathway of MCF-7 cells and further induced the formation of CSC-like phenotypes, ultimately promoting the proliferation and metastasis of MCF-7 cells. Therefore, SDF-1 may further be assessed as a potential target for gene therapy of breast cancer. IntroductionBreast cancer is one of the most common malignancies in women, with ~1.05 million new cases annually and 3.1% increasing rate (1,2). Currently, surgery, chemotherapy, radiotherapy and endocrine therapy are the mainstream clinical strategies for breast cancer, but 25% mortality rate still remains (3). The deterioration and poor prognosis of breast cancer are attributed to tumor invasion and metastasis (1). Epithelialmesenchymal transition (EMT) and EMT-induced acquisition of cancer stem cell (CSC)-like phenotypes are crucial for invasion and metastasis of tumor cells (4-7). Hence, finding the key molecules that regulate formation of EMT and CSCs is warranted to reveal the pathological progression of breast cancer and develop novel therapeutic approaches.The ...

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“…TAMs contribute to tumor growth and metastasis by secreting MMPs that promote extracellular matrix remodeling; angiogenic factors that increase blood vessel formation; and cytokines, chemokines, and growth factors that enhance tumor growth [18,19]. Specifically, TAMs have been reported to produce VEGF, epidermal growth factor, basic fibroblast growth factor, platelet-derived growth factor, IL-6, MCP-1, CXCL18, CXCL12, and YKL-40/CHI3L1 [16,[20][21][22][23][24][25]. YKL-40/CHI3L1 induces the expression of MCP-1/CCL2 and IL-8/CXCL2, which are chemoattractants for monocytes/ macrophages and neutrophils [16].…”

Section: Tumor-associated Inflammationmentioning

confidence: 99%

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

Libreros

Iragavarapu-Charyulu

2015

Journal of Leukocyte Biology

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Inflammation plays a vital role at different stages of tumor progression. The development of tumors is affected by inflammatory mediators produced by the tumor and the host. YKL-40/chitinase-3-like-1 protein is often upregulated in inflammation-associated diseases. With the use of chronic inflammatory disease systems, we describe the role of YKL-40/chitinase-3-like-1 protein in enhancing the inflammatory response and its implications in tumorigenesis. We also discuss how pre-existing inflammation enhances tumor growth and metastasis. In this mini-review, we highlight the effect of YKL-40/ chitinase-3-like-1 protein-associated inflammation in promoting tumor progression. J. Leukoc. Biol. 98: 931-936;

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Contribution of CXCL12 secretion to invasion of breast cancer cells

Cited by 99 publications

References 51 publications

Breast Cancer Prognostic Biomarker Using Attractor Metagenes and the FGD3–SUSD3 Metagene

Breast Cancer Prognostic Biomarker Using Attractor Metagenes and the FGD3–SUSD3 Metagene

Overexpression of SDF-1 activates the NF-κB pathway to induce epithelial to mesenchymal transition and cancer stem cell-like phenotypes of breast cancer cells

YKL-40/CHI3L1 drives inflammation on the road of tumor progression

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