Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12

Chung, Brile; Esmaeili, Ali A.; Gopalakrishna-Pillai, Sailesh; Murad, John P.; Andersen, Emily S.; Reddy, Naveen Kumar; Srinivasan, Gayathri; Armstrong, Brian; Chu, Caleb T.; Kim, Young; Tong, Teresa; Waisman, James; Yim, John H.; Badie, Behnam; Lee, Peter P.

doi:10.1038/s41523-017-0008-8

Cited by 60 publications

(43 citation statements)

References 31 publications

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“…Therefore, blocking the interaction between CXCR6-CXCL16 and/or CXCR4-CXCL12 significantly inhibits BC cell migration to brain metastatic BCAF aggregates. These data further support the important role of CXCL16 and CXCL12 in eliciting migration of CTCs to the brain metastatic niche [ 205 ].…”

Section: Role Of Bcafs In Bc Cell Dissemination and Metastasissupporting

confidence: 78%

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination

Avagliano

Fiume

Ruocco

et al. 2020

Cancers

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The stromal microenvironment regulates mammary gland development and tumorigenesis. In normal mammary glands, the stromal microenvironment encompasses the ducts and contains fibroblasts, the main regulators of branching morphogenesis. Understanding the way fibroblast signaling pathways regulate mammary gland development may offer insights into the mechanisms of breast cancer (BC) biology. In fact, the unregulated mammary fibroblast signaling pathways, associated with alterations in extracellular matrix (ECM) remodeling and branching morphogenesis, drive breast cancer microenvironment (BCM) remodeling and cancer growth. The BCM comprises a very heterogeneous tissue containing non-cancer stromal cells, namely, breast cancer-associated fibroblasts (BCAFs), which represent most of the tumor mass. Moreover, the different components of the BCM highly interact with cancer cells, thereby generating a tightly intertwined network. In particular, BC cells activate recruited normal fibroblasts in BCAFs, which, in turn, promote BCM remodeling and metastasis. Thus, comparing the roles of normal fibroblasts and BCAFs in the physiological and metastatic processes, could provide a deeper understanding of the signaling pathways regulating BC dissemination. Here, we review the latest literature describing the structure of the mammary gland and the BCM and summarize the influence of epithelial-mesenchymal transition (EpMT) and autophagy in BC dissemination. Finally, we discuss the roles of fibroblasts and BCAFs in mammary gland development and BCM remodeling, respectively.

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Section: Role Of Bcafs In Bc Cell Dissemination and Metastasissupporting

confidence: 78%

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination

Avagliano

Fiume

Ruocco

et al. 2020

Cancers

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“…In a previous study, our laboratory [10] showed that NIS could be generally identified by high expression of CD44 but low expressions of EPCAM and CD45. Epithelial cells and cancer cells express high levels of EPCAM but low levels of CD44 and CD45.…”

Section: Breast Tissue Samples and Bulk Rna-seqmentioning

confidence: 88%

Cell non-autonomous interactions during non-immune stromal progression in the breast tumor microenvironment

Utama

Bastian

Sadagopan

et al. 2019

Preprint

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The breast tumor microenvironment of primary and metastatic sites is a complex milieu of differing cell populations, consisting of tumor cells and the surrounding stroma. Despite recent progress in delineating the immune component of the stroma, the genomic expression landscape of the non-immune stroma (NIS) population and their role in mediating cancer progression and informing effective therapies are not well understood. Here we obtained 52 cell-sorted NIS and epithelial tissue samples across 37 patients from i) normal breast, ii) normal breast adjacent to primary tumor, iii) primary tumor, and iv) metastatic tumor sites. Deep RNA-seq revealed diverging gene expression profiles as the NIS evolves from normal to metastatic tumor tissue, with intra-patient normal-primary variation comparable to inter-patient variation. Significant expression changes between normal and adjacent normal tissue support the notion of a cancer field effect, but extended out to the NIS. Most differentially expressed proteincoding genes and lncRNAs were found to be associated with pattern formation, embryogenesis, and the epithelial-mesenchymal transition. We validated the protein expression changes of a novel candidate gene, C2orf88, by immunohistochemistry staining of representative tissues. Significant mutual information between epithelial ligand and NIS receptor gene expression, across primary and metastatic tissue, suggests a unidirectional model of molecular signaling between the two tissues. Furthermore, survival analyses of 827 luminal breast tumor samples demonstrated the predictive power of the NIS gene expression to inform clinical outcomes. Together, these results highlight the evolution of NIS gene expression in breast tumors and suggest novel therapeutic strategies targeting the microenvironment.

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“…were recently observed to be related to various in ammatory diseases, such as glomerulonephritis (42), pulmonary diseases (43), atherosclerosis (44), coronary artery disease (45), rheumatoid arthritis (46) and many in ammation-related cancers (47)(48)(49). At present, there are only four studies investigating the clinical associations between CXCL16 polymorphisms and atherosclerosis (32,50), coronary heart disease (39) and multiple sclerosis (51).…”

Section: Discussionmentioning

confidence: 99%

A Functional Variant of CXCL16 Is Associated with Predisposition to Sepsis and MODS in Trauma Patients

Sun

Zhang

Liu

et al. 2020

Preprint

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Background: CXC chemokine famliy genes play an important role in inflammatory and immune diseases. CXCL16 affects the occurrence and development of inflammation through leukocyte chemotaxis, leukocyte adhesion and endotoxin clearance. In this study, we selected a set of tag SNPs in the CXCL16 gene and investigated their clinical relevance to the development of sepsis and multiple organ dysfunction syndrome (MODS) in patients with major trauma in three independent Chinese Han populations. Methods: A total of 1,620 major trauma patients were enrolled in this study. Among these patients, 920 came from Chongqing in western China, 350 came from Zhejiang Province in eastern China, and 350 came from Guizhou Province in southern China. The improved multiplex ligation detection reaction (iMLDR) method was employed in the genotyping and genetic association analyses to determine the associations between CXCL16 haplotypes and sepsis morbidity rate and higher MOD scores in three cohorts. Results: The CXCL16 T123V181 haplotype was determined to be associated with increased risk for sepsis morbidity and higher MOD scores in the three cohorts. In vitro chemotactic experiments demonstrated that the T123V181 protein enhanced the chemotaxis of immunocytes. The adhesion ability of THP-1 cells expressing T123V181 to immunocytes was also stronger than those of cells with the other three haplotypes. T123 and V181 altered the structure of the CXCL16 active center, which resulted in changes in protein function and changes in the adhesion and chemotaxis of CXCL16-expressing immunocytes. These structural changes might be responsible for the increased incidence of sepsis and the higher MODS scores. Conclusions: We demonstrate that genetic variations in the CXCL16 gene regulate the sepsis morbidity rate, and we explore a paradigm for the prewarning diagnosis of sepsis tailored to the genetic information of individual patients. Trial registration: ClinicalTrials.gov, NCT01713205. Registered 18 October 2012, retrospectively registered.

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Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12

Cited by 60 publications

References 31 publications

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination

Cell non-autonomous interactions during non-immune stromal progression in the breast tumor microenvironment

A Functional Variant of CXCL16 Is Associated with Predisposition to Sepsis and MODS in Trauma Patients

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