Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

Prasmickaite, Lina; Tenstad, Ellen; Pettersen, Solveig; Jabeen, Shakila; Egeland, Eivind Valen; Nord, Silje; Pandya, Abhilash D.; Haugen, Mads H.; Kristensen, Vessela N.; Børresen‐Dale, Anne‐Lise; Engebråten, Olav; Mælandsmo, Gunhild Mari

doi:10.1002/1878-0261.12319

Cited by 32 publications

(29 citation statements)

References 54 publications

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“…S100A4 can not only be found in cancer cells but is also highly expressed in stromal cells of the tumour microenvironment (TME), such as fibroblasts, T-cells, macrophages, and neutrophils [ 81 , 96 ]. Extracellular S100A4 in the TME induces the release of pro-inflammatory factors (e.g., interleukin 6 (IL-6), interleukin 8 (IL-8), and C-X-C motif chemokine 10 (CXCL10)), which then converts monocytes into tumour-associated macrophages (TAMs), resulting in metastasis and drug resistance [ 97 ].…”

Section: S100 Proteins In Cancermentioning

confidence: 99%

Friend or Foe: S100 Proteins in Cancer

Allgöwer

Kretz

Karstedt

et al. 2020

Cancers

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S100 proteins are widely expressed small molecular EF-hand calcium-binding proteins of vertebrates, which are involved in numerous cellular processes, such as Ca2+ homeostasis, proliferation, apoptosis, differentiation, and inflammation. Although the complex network of S100 signalling is by far not fully deciphered, several S100 family members could be linked to a variety of diseases, such as inflammatory disorders, neurological diseases, and also cancer. The research of the past decades revealed that S100 proteins play a crucial role in the development and progression of many cancer types, such as breast cancer, lung cancer, and melanoma. Hence, S100 family members have also been shown to be promising diagnostic markers and possible novel targets for therapy. However, the current knowledge of S100 proteins is limited and more attention to this unique group of proteins is needed. Therefore, this review article summarises S100 proteins and their relation in different cancer types, while also providing an overview of novel therapeutic strategies for targeting S100 proteins for cancer treatment.

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Section: S100 Proteins In Cancermentioning

confidence: 99%

Friend or Foe: S100 Proteins in Cancer

Allgöwer

Kretz

Karstedt

et al. 2020

Cancers

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“…Overexpression of some inflammatory factors may paradoxically increase promotion of the immunosuppressive phenotype. In breast cancer (basal-like BCC), the S100 calcium-binding protein A4 (S100A4) promotes monocyte differentiation and polarization towards M2 phenotype macrophages as well as induces increased expression of interleukin-6 (IL6) and IL8 in macrophages [57].…”

Section: Tumor Associated Macrophagesmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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“…Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the tumor microenvironment, which have been shown to be linked to poor prognosis and therapeutic resistance [ 63 ]. It was demonstrated ex vivo that BC cells secret factors that modulate macrophage differentiation toward the M2 phenotype and correlate with recurrence-free survival, therapeutic efficacy, and patient outcome [ 64 ].…”

Section: Role Of Innate Cells In Breast Cancermentioning

confidence: 99%

“…In the aggressive triple-negative/basal-like subgroup, S100A4 was demonstrated to activate BC cells in various ways such as an increase in the secretion of pro-inflammatory cytokines, which, consequently, convert monocytes to macrophages. Another suggested mechanism would be promoting pro-tumorigenic activities such as stimulated epithelial–mesenchymal transition, proliferation, chemoresistance, and motility of cancer cells [ 63 ].…”

Section: Role Of Innate Cells In Breast Cancermentioning

confidence: 99%

Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

Shihab

Khalil

Elemam

et al. 2020

Cancers

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The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.

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Basal‐like breast cancer engages tumor‐supportive macrophages via secreted factors induced by extracellular S100A4

Cited by 32 publications

References 54 publications

Friend or Foe: S100 Proteins in Cancer

Friend or Foe: S100 Proteins in Cancer

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

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