Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties

Bettum, Ingrid J.; Vasiliauskaite, Kotryna; Nygaard, Vigdis; Clancy, Trevor; Pettersen, Solveig; Tenstad, Ellen; Mælandsmo, Gunhild Mari; Prasmickaite, Lina

doi:10.1016/j.canlet.2013.10.036

Cited by 51 publications

(44 citation statements)

References 246 publications

(263 reference statements)

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“…The protein stock had no detectable endotoxins as assayed by Lonza Biosciences. The specificity of rS100A4 to induce cytokines has been validated previously using of a S100A4‐blocking antibody (Bettum et al ., 2014). Granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and macrophage colony‐stimulating factor (M‐CSF) were purchased from R&D Systems (Oxon, UK).…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we have demonstrated that macrophage phenotype and functions can be modulated by factors secreted by aggressive melanoma cells that are stimulated with extracellular S100A4 (Bettum et al ., 2014). S100A4 is a small, Ca 2+ ‐binding protein strongly associated with metastasis and poor prognosis in various cancers (Boye and Maelandsmo, 2009; Mishra et al ., 2011; Rudland et al ., 2000) and also involved in inflammatory disorders (Cerezo et al ., 2011; Grigorian et al ., 2008).…”

Section: Introductionmentioning

confidence: 99%

“…S100A4 is a small, Ca 2+ ‐binding protein strongly associated with metastasis and poor prognosis in various cancers (Boye and Maelandsmo, 2009; Mishra et al ., 2011; Rudland et al ., 2000) and also involved in inflammatory disorders (Cerezo et al ., 2011; Grigorian et al ., 2008). S100A4 is expressed not only in tumor cells, but also in various stromal cells, and secreted into the extracellular space (Bettum et al ., 2014; Cabezon et al ., 2007). Both endogenous and extracellular S100A4 have been linked to metastasis.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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The tumor microenvironment (TME) may influence both cancer progression and therapeutic response. In breast cancer, particularly in the aggressive triple‐negative/basal‐like subgroup, patient outcome is strongly associated with the tumor's inflammatory profile. Tumor‐associated macrophages (TAMs) are among the most abundant immune cells in the TME, shown to be linked to poor prognosis and therapeutic resistance. In this study, we investigated the effect of the metastasis‐ and inflammation‐associated microenvironmental factor S100A4 on breast cancer cells (BCCs) of different subtypes and explored their further interactions with myeloid cells. We demonstrated that extracellular S100A4 activates BCCs, particularly the basal‐like subtype, to elevate secretion of pro‐inflammatory cytokines. The secreted factors promoted conversion of monocytes to TAM‐like cells that exhibited protumorigenic activities: stimulated epithelial–mesenchymal transition, proliferation, chemoresistance, and motility in cancer cells. In conclusion, we have shown that extracellular S100A4 instigates a tumor‐supportive microenvironment, involving a network of cytokines and TAM‐like cells, which was particularly characteristic for basal‐like BCCs and potentiated their aggressive properties. The S100A4–BCC–TAM interaction cascade could be an important contributor to the aggressive behavior of this subtype and should be further explored for therapeutic targeting.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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“…Schematic pathway for bladder cancer invasiveness development (Kader et al, 2007;Pei et al, 2014;Donmez et al, 2009;Bettum et al, 2014).…”

Section: Appendicesmentioning

confidence: 99%

Disease map-based biomarker selection and pre-validation for bladder cancer diagnostic

et al. 2015

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“…Metastasis-associated protein 1 (MTA1) is a human protein that is encoded by the MTA1 gene (8,9). MTA1 is a protein that has been associated with the metastatic state of various cancer types (10)(11)(12)(13)(14). MTA1 promotes tumor invasion by the downregulation of E-cadherin in human esophageal squamous cell carcinoma cells (10).…”

Section: Introductionmentioning

confidence: 99%

Endocrine MPA enhances the effects of TAC chemotherapy on improvement of prognosis and increase in long-term survival rates for patients with endometrial cancer

Yuan¹,

Wang²,

Xue³

et al. 2015

Oncology Letters

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Abstract. The aim of the present study was to investigate the effect of taxol, adriamycin and carboplatin (TAC) chemotherapy combined with endocrine medroxyprogesterone acetate (MPA) therapy for the treatment of patients with endometrial cancer. A retrospective analysis of 124 patients with endometrial cancer was performed by dividing the cohort into an experimental and control group. The 64 patients in the experimental group received TAC and MPA chemotherapy, whereas the 60 patients in the control group were treated with TAC chemotherapy only. Tissue samples scraped from the uterus were used to extract the total proteins and RNAs for the western blot and reverse transcription-quantitative polymerase chain reaction analyses, respectively. All the patients were followed up for 20-45 months, during which time prognostic data, and one-to three-year survival rates were recorded and compared. The rate of recurrence or metastasis was significantly lower in the experimental group compared with that in the control group (P<0.05) and the three-year survival rate of the experimental group was significantly higher than that of the control group (P<0.05). Furthermore, the mean metastasis-associated 1 (MTA1) protein and RNA expression levels were significantly lower in the experimental group compared with the control group (P<0.05), exhibiting ~30 and ~15% of the levels in the control group, respectively. Therefore, a treatment strategy of TAC chemotherapy combined with endocrine MPA therapy appears to effectively improve the prognosis and increase the long-term survival rates of patients with endometrial cancer. Such an enhancing effect may be mediated by the transcriptional downregulation of MTA1 expression. IntroductionEndometrial cancer is a common type of malignant gynecological disease that predominantly occurs in post-menopausal females, aged 50-60 years. It accounts for 20-30% of cases of female cancer, with the incidence rate demonstrating an increasing trend in recent years (1). Tumors in endometrial cancer patients at clinical stages I/II exhibit a low degree of differentiation and invasive ability, therefore, good results can be obtained using surgical intervention. By contrast, tumors in patients at stages III/IV exhibit a higher degree of malignancy and differentiation, therefore, surgical treatments are only able to reduce tumor volume. Instead, adjuvant endocrine therapy, radiotherapy, and chemotherapy are typically administered for patients at stages III and IV to effectively improve the survival rate (2-4).The taxol, adriamycin and carboplatin (TAC) chemotherapy regimen has gradually been utilized for the treatment of patients with advanced endometrial cancer. Compared with the traditional adriamycin/cisplatin and cyclophosphamide/adriamycin/cisplatin regimens, the effect of the TAC regimen is more pronounced, causing fewer side effects in patients. In particular, TAC exhibits lower hematological toxicity, thus, resulting in more comprehensive treatment and improved recovery for patients (5).Endocrine thera...

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Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties

Cited by 51 publications

References 246 publications

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

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

Disease map-based biomarker selection and pre-validation for bladder cancer diagnostic

Endocrine MPA enhances the effects of TAC chemotherapy on improvement of prognosis and increase in long-term survival rates for patients with endometrial cancer

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