IL-6-mediated cross-talk between human preadipocytes and ductal carcinoma in situ in breast cancer progression

Kim, Hoe Suk; Jung, Minji; Choi, Sul Ki; Woo, Jisu; Piao, Yin Ji; Hwang, Eunmi; Kim, Hyelim; Kim, Seung Ja; Moon, Woo Kyung

doi:10.1186/s13046-018-0867-3

Cited by 37 publications

(27 citation statements)

References 34 publications

(36 reference statements)

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“…There are cancer-associated adipocytes (CAA) around breast cancer tissue. When adipocytes are co-cultured with breast cancer cells, the expression and secretion of IL-6 in adipocytes increase, promoting the invasion and migration of cancer cells [25–27]. When IL-6R is blocked by anti-IL-6R antibody, the metastasis of breast cancer induced by IL-6 is reversed [28, 29].…”

Section: Caas Secrete Inflammatory Factors That Modify the Behavior Omentioning

confidence: 99%

Cancer-associated adipocytes: key players in breast cancer progression

et al. 2019

J Hematol Oncol

298

283

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Adipocytes are one of the primary stromal cells in many tissues, and they are considered to play an active role in the tumor microenvironment. Cancer-associated adipocytes (CAAs) are not only found adjacent to cancer cells, but also communicate with cancer cells through releasing various factors that can mediate local and systemic effects. The adipocyte-cancer cell crosstalk leads to phenotypical and functional changes of both cell types, which can further enhance tumor progression. Indeed, obesity, which is associated with an increase in adipose mass and an alteration of adipose tissue, is becoming pandemic in some countries and it is now considered to be an independent risk factor for cancer progression. In this review, we focus on the potential mechanisms involved with special attention to the adipocyte-cancer cell circle in breast cancer. We envisage that besides having a direct impact on tumor cells, CAAs systemically preconditions the tumor microenvironment by favoring anti-tumor immunity. A better understanding of cancer-associated adipocytes and the key molecular events in the adipocyte-cancer cell crosstalk will provide insights into tumor biology and permit the optimization of therapeutic strategies.

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Section: Caas Secrete Inflammatory Factors That Modify the Behavior Omentioning

confidence: 99%

Cancer-associated adipocytes: key players in breast cancer progression

et al. 2019

J Hematol Oncol

298

283

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“…Adipocytes also play an active role in the TME and cancer-associated adipocytes have smaller lipid droplets and a more fibroblast-like phenotype, compared to normal adipocytes [ 140 ]. When preadipocytes were cocultured with breast cancer cells, there was enhanced CAF marker expression and IL-6 secretion, which promotes tumourigenesis; although the activation of Notch was not investigated [ 141 ]. RNA within exosomes released from stromal cells stimulated STAT1-dependent antiviral response signalling in breast cancer cells.…”

Section: Notch Signalling In the Tumour Microenvironment: Interactmentioning

confidence: 99%

Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives

Moore

Annett

McClements

et al. 2020

Cells

103

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Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, lung and adenoid cystic carcinoma. Moreover, upregulation of Notch receptors and ligands and aberrant Notch signalling is frequently observed in cancer. It is involved in cancer hallmarks including proliferation, survival, migration, angiogenesis, cancer stem cell renewal, metastasis and drug resistance. It is a key component of cell-to-cell interactions between cancer cells and cells of the tumour microenvironment, such as endothelial cells, immune cells and fibroblasts. Notch displays diverse crosstalk with many other oncogenic signalling pathways, and may drive acquired resistance to targeted therapies as well as resistance to standard chemo/radiation therapy. The past 10 years have seen the emergence of different classes of drugs therapeutically targeting Notch including receptor/ligand antibodies, gamma secretase inhibitors (GSI) and most recently, the development of Notch transcription complex inhibitors. It is an exciting time for Notch research with over 70 cancer clinical trials registered and the first-ever Phase III trial of a Notch GSI, nirogacestat, currently at the recruitment stage.

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“…The upgraded serum levels of leptin have also been associated with higher pathological grade and aggressive phenotypes in breast cancer patients [139]. Produced by adipose tissues, IL-6 is more secreted in CAAs compared with other adipocytes [131], and it has also been shown to promote cancer progression when adipocytes are co-cultured with breast cancer cells [140]. Furthermore, it has also been demonstrated that IL-6 production can regulate cancer cell survival, immune suppression and drug resistance by JAK phosphorylation and STAT3 activation [141].…”

Section: Cancer-associated Adipocytesmentioning

confidence: 99%

“…Pathobiology 2020;87:[125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142] …”

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The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

et al. 2020

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Heterogeneity in breast carcinomas can be appreciated at various levels, from morphology to molecular alterations, and there are well-known genotypic-phenotypic correlations. Clinical decision-making is strictly focused on the evaluation of tumor cells and is based on the assessment of hormone receptors and of the HER2 status, by means of a combination of immunohistochemical and in situ hybridization techniques. The tumor microenvironment (TME) also shows a multifaceted nature stemming from the different actors populating the intratumoral and the peritumoral stroma of breast carcinomas. Of note, we have now evidence that tumor-infiltrating lymphocytes (TILs) are clinically meaningful as their quantification in the intratumoral stroma strongly correlates with good prognosis, in particular in triple-negative and HER2-positive breast cancer patients. Nevertheless, TILs are just one of the many actors orchestrating the com-plexity of the TME, which is populated by immune and nonimmune cells (cancer-associated fibroblasts, cancer-associated adipocytes), as well as non-cellular components such as chemical inflammation mediators. In this review article we will overview the main features of the distinct cell compartments by discussing (i) the potential impact the TME may have on the prognostic stratification of breast cancers and (ii) the possible predictive value of some markers in the context of immunotherapy in light of the recent results of phase III studies in advanced and early triple-negative breast cancer patients.

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IL-6-mediated cross-talk between human preadipocytes and ductal carcinoma in situ in breast cancer progression

Cited by 37 publications

References 34 publications

Cancer-associated adipocytes: key players in breast cancer progression

Cancer-associated adipocytes: key players in breast cancer progression

Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives

The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

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