Cancer-associated fibroblasts: A multifaceted driver of breast cancer progression

Luo, Haojun; Tu, Gang; Liu, Zhimin; Liu, Manran

doi:10.1016/j.canlet.2015.02.018

Cited by 177 publications

(130 citation statements)

References 147 publications

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“…αSMA plays a role in cell motility as it is a major constituent of the cytoskeleton and is expressed by myofibroblasts during wound healing as well as cancer-associated fibroblasts (CAFs) [2]. Importantly, we could further validate our observations by an IHC analysis of αSMA protein levels, which were significantly upregulated in stromal cells of the tumour but not in normal stroma ( Figures 3A, 4A and 5A).…”

Section: Acta2/αsmasupporting

confidence: 68%

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Ettlin

Clementi

Amini

et al. 2018

Journal of Comparative Pathology

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Cancer-associated stroma (CAS) plays a key role in cancer initiation and progression. Spontaneously occurring canine mammary carcinomas are viewed as excellent models of human breast carcinomas. Considering the importance of CAS for human cancer, it likely plays a central role in canine tumours as well. So far, however, canine CAS lacks characterisation, and it remains unclear whether the biology between CAS from canine and human tumours is comparable. In this proof-of-principle study, using laser-capture microdissection, we isolated CAS and normal stroma from 13 formalin-fixed paraffin embedded canine simple mammary carcinomas and analysed the expression of seven known human CAS markers by RT-qPCR (Reverse Transcription quantitative PCR) and validated some targets by immunohistochemistry. We found that Col1a1 (Collagen1α1), αSMA (alpha Smooth Muscle Actin), FAP (Fibroblast activation protein), PDGFRβ (Platelet-derived growth factor receptor beta), and Caveolin-1 were significantly upregulated in canine CAS, and the expression of CXCL12 (Stromal cell derived factor 1) significantly decreased, whereas MMP2 (Matrix Metalloproteinase 1) and IL6 (Interleukin 6) did not change. Our results suggest strong similarities in CAS biology in canine and human mammary carcinomas but also reveal some differences. To the best of our knowledge, this is the first report to provide a comprehensive expression analysis of the most important CAS markers in canine simple mammary carcinomas and further supports the validity of the dog as model for human cancer.

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Section: Acta2/αsmasupporting

confidence: 68%

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Ettlin

Clementi

Amini

et al. 2018

Journal of Comparative Pathology

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“…TAFs were found to contribute to the inflammatory immunosuppressive milieu within tumor microenvironment, probably through the overexpression and upregulation of fibroblast activation protein-α, rapid hypoxic necrosis of tumor, activation of stromal cells, or cytotoxicity of IFNγ or TNFα-mediated CD8+ T cells [22]. TAMs and TAFs serve as an important source of tumor-promoting cytokines and growth factors and regulate biological behaviors of cancer cells through nuclear factorkappaB (NF-κB)-dependent signal pathway [23]. Of those, TAFs were suspected to coordinate events responsible for cancer cell growth and survival, angiogenesis, or metastasis [24].…”

Section: Roles Of Inflammatory Cells In Cancer-related Inflammationmentioning

confidence: 99%

Targeting roles of inflammatory microenvironment in lung cancer and metastasis

Shi

Wang

Hou

et al. 2015

Cancer Metastasis Rev

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Inflammatory cells and mediators are essential components in tumor microenvironment and play decisive roles in the initiation, proliferation, survival, promotion, invasion, or metastasis of lung cancer. Clinical and epidemiologic studies suggested a strong association between inflammation and lung cancer and an influence of immune surveillances and tumor responses to chemotherapeutic drugs, although roles of inflammation in lung cancer remain unclear. The present review outlined roles of inflammation in lung cancer, with particular focus on inflammatory components, types, biomarkers, or principal mechanisms by which the inflammation contributes to the development of lung cancer. The cancer-associated inflammatory cells (CICs) should be furthermore defined and include cancer-specific and interacted cells with inflammatory or inflammation-like characteristics, e.g., innate or adaptive immune cells and cancer tissue cells. We also discuss targeting potentials of inflammation in the prevention and treatment of lung cancer. The diversity of cancer-related inflammatory microenvironment is instrumental to design novel therapeutic approaches for lung cancer.

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“…We therefore designed our study using cell types that were likely to influence each other’s gene expression when in co- and tri-culture. Because interactions between cancer, mesenchymal (Downey et al 2014; Amornsupak et al 2014; Luo et al 2015), and immune compartments (Nagalla et al 2013; Maley et al 2015; Stewart et al 2012; Tabariès et al 2015; Goswami et al 2005) play critical roles in a number of aspects of cellular phenotypic and functional modification in cancer progression, our models included combinations of one of two distinct breast cancers cell lines, SKBR3 and BT474, with the bone marrow stromal cell line, HS5, and ThP1 monocytes differentiated to M2, TAM-like macrophages. SKBR3 and BT474 are representative of the HER2-expressing subtype of breast cancer which comprises approximately 20 percentage of breast cancers and in which a stromal-derived gene signature was shown to have strongest prognostic value in clinical samples (Finak et al 2008).…”

Section: Resultsmentioning

confidence: 99%

Transitions from mono- to co- to tri-culture uniquely affect gene expression in breast cancer, stromal, and immune compartments

Regier

Maccoux

Weinberger

et al. 2016

Biomed Microdevices

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Heterotypic interactions in cancer microenvironments play important roles in disease initiation, progression, and spread. Co-culture is the predominant approach used in dissecting paracrine interactions between tumor and stromal cells, but functional results from simple co-cultures frequently fail to correlate to in vivo conditions. Though complex heterotypic in vitro models have improved functional relevance, there is little systematic knowledge of how multi-culture parameters influence this recapitulation. We therefore have employed a more iterative approach to investigate the influence of increasing model complexity; increased heterotypic complexity specifically. Here we describe how the compartmentalized and microscale elements of our multi-culture device allowed us to obtain gene expression data from one cell type at a time in a heterotypic culture where cells communicated through paracrine interactions. With our device we generated a large dataset comprised of cell type specific gene-expression patterns for cultures of increasing complexity (three cell types in mono-, co-, or tri-culture) not readily accessible in other systems. Principal component analysis indicated that gene expression was changed in co-culture but was often more strongly altered in tri-culture as compared to mono-culture. Our analysis revealed that cell type identity and the complexity around it (mono-, co-, or tri-culture) influence gene regulation. We also observed evidence of complementary regulation between cell types in the same heterotypic culture. Here we demonstrate the utility of our platform in providing insight into how tumor and stromal cells respond to microenvironments of varying complexities highlighting the expanding importance of heterotypic cultures that go beyond conventional co-culture.

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Cancer-associated fibroblasts: A multifaceted driver of breast cancer progression

Cited by 177 publications

References 147 publications

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Analysis of Gene Expression Signatures in Cancer-Associated Stroma from Canine Mammary Tumours Reveals Molecular Homology to Human Breast Carcinomas

Targeting roles of inflammatory microenvironment in lung cancer and metastasis

Transitions from mono- to co- to tri-culture uniquely affect gene expression in breast cancer, stromal, and immune compartments

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