Tumor-extracellular matrix interactions: Identification of tools associated with breast cancer progression

Giussani, Marta; Merlino, Giuseppe; Cappelletti, Vera; Tagliabue, Elda; Daidone, Maria Grazia

doi:10.1016/j.semcancer.2015.09.012

Cited by 133 publications

(116 citation statements)

References 83 publications

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“…The stromal microenvironment of DCIS largely consists of an insoluble ECM, comprised a complex mixture of glycoproteins, proteins, proteoglycans and polysaccharides 41. Also within the ECM surrounding the duct are populations of adipocytes, fibroblasts, mesenchymal stem cells, endothelial and immune cells that produce a multitude of growth factors and cytokines.…”

Section: Tumour Cell Extrinsic Factors Involved In Dcis Progressionmentioning

confidence: 99%

Identifying progression predictors of breast ductal carcinoma in situ

et al. 2016

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Ductal carcinoma in situ (DCIS) refers to neoplastic epithelial cells proliferating within the mammary ducts of the breast, which have not breached the basement membrane nor invaded surrounding tissues. Traditional thinking holds that DCIS represents an early step in a linear progression towards invasive ductal carcinoma (IDC). However, as only approximately half of DCIS cases progress to IDC, important questions around the key determinants of malignant progression need to be answered. Recent studies have revealed that molecular differences between DCIS and IDC cells are not found at the genomic level; instead, altered patterns of gene expression and post-translational regulation lead to distinct transcriptomic and proteomic profiles. Therefore, understanding malignant progression will require a different approach that takes into account the diverse tumour cell extrinsic factors driving changes in tumour cell gene expression necessary for the invasive phenotype. Here, we review the roles of the tumour stroma (including mesenchymal cells, immune cells and the extracellular matrix) and myoepithelial cells in malignant progression and make a case for a more integrated approach to the study and assessment of DCIS and its progression, or lack thereof, to invasive disease.

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Section: Tumour Cell Extrinsic Factors Involved In Dcis Progressionmentioning

confidence: 99%

Identifying progression predictors of breast ductal carcinoma in situ

et al. 2016

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“…Tumours are complex entities that include genetically and metabolically aberrant cancer cells, genetically stable stromal cells, and infiltrating immune cells. They are functionally dependent on the acidic, hypoxic, and poorly perfused serum-deprived microenvironment that surrounds them for cancer progression to occur (12,13).…”

Section: Introductionmentioning

confidence: 99%

Na + /H + exchanger-mediated hydrogen ion extrusion as a carcinogenic signal in triple-negative breast cancer etiopathogenesis and prospects for its inhibition in therapeutics

Amith

Fliegel

2017

Seminars in Cancer Biology

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Please cite this article as: Amith Schammim Ray, Fliegel Larry.Na+/H+ exchangermediated hydrogen ion extrusion as a carcinogenic signal in triple-negative breast cancer etiopathogenesis and prospects for its inhibition in therapeutics.Seminars in Cancer Biology http://dx.doi. org/10.1016/j.semcancer.2017.01.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Abstract (250 words):Breast cancer is the leading cause of cancer-related death in women in Europe and North America, and metastasis is the primary cause of fatality in patients with breast cancer. While some breast cancers are quite treatable, the triple-negative breast cancers are more metastatic and resistant to chemotherapy. There is clearly an urgent need for better treatments for this form of the disease. Breast cancer is characterized by genetically complex intra-tumour heterogeneity, particularly within the triple-negative clinical subtype. This complicates treatment options, so the development of specifically targeted chemotherapy for less treatable forms is critical.Dysregulation of pH homeostasis is a common factor in breast tumour cells. This occurs in concert with a metabolic switch to aerobic glycolysis that occurs at the onset of oncogenic transformation. The Na + /H + exchanger isoform 1 (NHE1) is the major pH regulatory protein involved in the increased proton extrusion of breast cancer cells. Its increased activity results in intracellular alkalinisation and extracellular acidification that drives cancer progression. The acidification of the extracellular tumour microenvironment also contributes to the development of chemotherapy resistance. In this review, we outline the role of H + as a carcinogenic signal and the role and regulation of NHE1 as a trigger for metastasis. We review recent evidence supporting the use of pharmacological inhibitors of NHE1 as a viable treatment option for triplenegative breast cancer.

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“…Although many ECM components have been identiied as relevant factors in breast cancer progression, evaluation and targeting of a single molecule appears to have limited usefulness in predicting therapeutic response. This might atribute to the large number of ECM components, which, even if likely redundant, collectively contribute to distinctive physical, biochemical, and biomechanical properties of the tumor microenvironment [8]. In gene expression, proiles of breast cancer-associated ibroblasts identify distinct stromal paterns with prognostic implication, and the expression proiles of some extracellular matrix genes provide prognostic information of patients at risk of clinical progression and/or predictive signiicance for treatment eicacy.…”

Section: Introductionmentioning

confidence: 99%

Immune Regulation in Breast Cancer Metastasis and Immunotherapy

Dai¹

2017

Breast Cancer - From Biology to Medicine

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There are signiicant alterations in the tumor surrounding stromal cells in addition to the cancer cells in tumor microenvironment. Tumor cells can metastasize by acquiring the ability to escape immune control and surveillance. A decline in the ability of the immune cells to recognize and kill the tumor leads to tumor relapse or metastasis after primary treatment. Comprehensive review in this chapter will be conducted to further investigate into the mechanism of immune evasion in metastatic tumor microenvironment. The immune cells, stromal cells, extracellular matrix protein/component, and their interaction will be reviewed and summarized. Breast cancer has not been previously viewed as a particularly immunogenic type of tumor. Nevertheless, immune parameters have been increasingly studied in breast cancer, and accumulating data show that they are relevant for the development and progression of this tumor type. Consequently, immunotherapies of breast cancer are now tested in diferent clinical trials. The prospect of immunotherapy in metastatic breast cancer will be introduced. The importance of host-targeted modulation/therapy will be increased in addition to cancer-targeted strategies. We have to beter deine subpopulations of breast cancer patients to optimize the immunological way to overcome the cancer metastasis.

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Tumor-extracellular matrix interactions: Identification of tools associated with breast cancer progression

Cited by 133 publications

References 83 publications

Identifying progression predictors of breast ductal carcinoma in situ

Identifying progression predictors of breast ductal carcinoma in situ

Na + /H + exchanger-mediated hydrogen ion extrusion as a carcinogenic signal in triple-negative breast cancer etiopathogenesis and prospects for its inhibition in therapeutics

Immune Regulation in Breast Cancer Metastasis and Immunotherapy

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