scholarly journals CD73 facilitates EMT progression and promotes lung metastases in triple-negative breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nataliia Petruk ◽  
Sanni Tuominen ◽  
Malin Åkerfelt ◽  
Jesse Mattsson ◽  
Jouko Sandholm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Lung Metastases ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
Cell Protrusion

AbstractCD73 is a cell surface ecto-5′-nucleotidase, which converts extracellular adenosine monophosphate to adenosine. High tumor CD73 expression is associated with poor outcome among triple-negative breast cancer (TNBC) patients. Here we investigated the mechanisms by which CD73 might contribute to TNBC progression. This was done by inhibiting CD73 with adenosine 5′-(α, β-methylene) diphosphate (APCP) in MDA-MB-231 or 4T1 TNBC cells or through shRNA-silencing (sh-CD73). Effects of such inhibition on cell behavior was then studied in normoxia and hypoxia in vitro and in an orthotopic mouse model in vivo. CD73 inhibition, through shRNA or APCP significantly decreased cellular viability and migration in normoxia. Inhibition of CD73 also resulted in suppression of hypoxia-induced increase in viability and prevented cell protrusion elongation in both normoxia and hypoxia in cancer cells. Sh-CD73 4T1 cells formed significantly smaller and less invasive 3D organoids in vitro, and significantly smaller orthotopic tumors and less lung metastases than control shRNA cells in vivo. CD73 suppression increased E-cadherin and decreased vimentin expression in vitro and in vivo, proposing maintenance of a more epithelial phenotype. In conclusion, our results suggest that CD73 may promote early steps of tumor progression, possibly through facilitating epithelial–mesenchymal transition.

scholarly journals An in vitro–in vivo model of epithelial mesenchymal transition in triple negative breast cancer

2012 ◽  
Vol 9 (1-2) ◽  
pp. e35-e40 ◽  
Author(s):  
Yubo Zhai ◽  
Julia Santucci-Pereira ◽  
Ricardo Lopez de Cicco ◽  
Irma H. Russo ◽  
Jose Russo
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
In Vivo Model ◽  
Mesenchymal Transition

The Potential of Natural Products in the Treatment of Triple-Negative Breast Cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Danny Yu Jia Ke ◽  
Sara El-Sahli ◽  
Lisheng Wang
Keyword(s):  
Breast Cancer ◽  
Natural Products ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Human Populations ◽  
Case Control Studies ◽  
Mesenchymal Transition

Abstract: Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks receptors for targeted therapy. Consequently, chemotherapy is currently the mainstay of systemic treatment options. However, the enrichment of cancer stem cells (CSC, a subpopulation with stem-cell characteristics and tumor-initiating propensity) promotes chemo-resistance and tumorigenesis, resulting in cancer recurrence and relapse. Furthermore, toxic side effects of chemotherapeutics reduce patient wellbeing. Natural products, specifically compounds derived from plants, have the potential to treat TNBC and target CSCs by inhibiting CSC signaling pathways. Literature evidence from six promising compounds were reviewed, including sulforaphane, curcumin, genistein, resveratrol, lycopene, and epigallocatechin-3-gallate. These compounds have been shown to promote cell cycle arrest and apoptosis in TNBC cells. They also could inhibit the epithelial-mesenchymal transition (EMT) that plays an important role in metastasis. In addition, those natural compounds have been found to inhibit pathways important for CSCs, such as NF-κB, PI3K/Akt/mTOR, Notch 1, Wnt/β-catenin, and YAP. Clinicals trials conducted on these compounds have shown varying degrees of effectiveness. Epidemiological case-control studies for the compounds commonly consumed in certain human populations have also been summarized. While in vivo and in vitro data are promising, further basic and clinical investigations are required. Likely, natural products in combination with other drugs may hold great potential to improve TNBC treatment efficacy and patient outcomes.

scholarly journals LncRNA DLX6-AS1 Contributes to Epithelial–Mesenchymal Transition and Cisplatin Resistance in Triple-negative Breast Cancer via Modulating Mir-199b-5p/Paxillin Axis

2020 ◽  
Vol 29 ◽  
pp. 096368972092998 ◽  
Author(s):  
Chuang Du ◽  
Yan Wang ◽  
Yingying Zhang ◽  
Jianhua Zhang ◽  
Linfeng Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Drug Resistance ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cisplatin Resistance ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Expression Levels

Triple-negative breast cancer (TNBC) is one of the most aggressive cancer types with high recurrence, metastasis, and drug resistance. Recent studies report that long noncoding RNAs (lncRNAs)-mediated competing endogenous RNAs (ceRNA) play an important role in tumorigenesis and drug resistance of TNBC. Although elevated lncRNA DLX6 antisense RNA 1 (DLX6-AS1) has been observed to promote carcinogenesis in various cancers, the role in TNBC remained unclear. In this study, expression levels of DLX6-AS1 were increased in TNBC tissues and cell lines when compared with normal tissues or breast fibroblast cells which were determined by quantitative real-time PCR (RT-qPCR). Then, CCK-8 assay, cell colony formation assay and western blot were performed in CAL-51 cells transfected with siRNAs of DLX6-AS1 or MDA-MB-231 cells transfected with DLX6-AS1 over expression plasmids. Knock down of DLX6-AS1 inhibited cell proliferation, epithelial-mesenchymal transition (EMT), decreased expression levels of BCL2 apoptosis regulator (Bcl-2), Snail family transcriptional repressor 1 (Snail) as well as N-cadherin and decreased expression levels of cleaved caspase-3, γ-catenin as well as E-cadherin, while up regulation of DLX6-AS1 had the opposite effect. Besides, knockdown of DLX6-AS1 in CAL-51 cells or up regulation of DLX6-AS1 in MDA-MB-231 cells also decreased or increased cisplatin resistance of those cells analyzed by MTT assay. Moreover, by using dual luciferase reporter assay, RNA immunoprecipitation and RNA pull down assay, a ceRNA which was consisted by lncRNA DLX6-AS1, microRNA-199b-5p (miR-199b-5p) and paxillin (PXN) was identified. And DLX6-AS1 function through miR-199b-5p/PXN in TNBC cells. Finally, results of xenograft experiments using nude mice showed that DLX6-AS1 regulated cell proliferation, EMT and cisplatin resistance by miR-199b-5p/PXN axis in vivo. In brief, DLX6-AS1 promoted cell proliferation, EMT, and cisplatin resistance through miR-199b-5p/PXN signaling in TNBC in vitro and in vivo.

scholarly journals CircNR3C2 promotes HRD1-mediated tumor-suppressive effect via sponging miR-513a-3p in triple-negative breast cancer

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ya Fan ◽  
Jia Wang ◽  
Wen Jin ◽  
Yifei Sun ◽  
Yuemei Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Rna Sequencing ◽  
Cancer Progression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Proteasomal Degradation ◽  
Circular Rnas ◽  
Mesenchymal Transition

Abstract Background E3 ubiquitin ligase HRD1 (HMG-CoA reductase degradation protein 1, alias synoviolin with SYVN1 as the official gene symbol) was found downregulated and acting as a tumor suppressor in breast cancer, while the exact expression profile of HRD1 in different breast cancer subtypes remains unknown. Recent studies characterized circular RNAs (circRNAs) playing an regulatory role as miRNA sponge in tumor progression, presenting a new viewpoint for the post-transcriptional regulation of cancer-related genes. Methods Examination of the expression of HRD1 protein and mRNA was implemented using public microarray/RNA-sequencing datasets and breast cancer tissues/cell lines. Based on public RNA-sequencing results, online databases and enrichment/clustering analyses were used to predict the specific combinations of circRNA/miRNA that potentially govern HRD1 expression. Gain-of-function and rescue experiments in vitro and in vivo were executed to evaluate the suppressive effects of circNR3C2 on breast cancer progression through HRD1-mediated proteasomal degradation of Vimentin, which was identified using immunoblotting, immunoprecipitation, and in vitro ubiquitination assays. Results HRD1 is significantly underexpressed in triple-negative breast cancer (TNBC) against other subtypes and has an inverse correlation with Vimentin, inhibiting the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) process of breast cancer cells via inducing polyubiquitination-mediated proteasomal degradation of Vimentin. CircNR3C2 (hsa_circ_0071127) is also remarkably downregulated in TNBC, negatively correlated with the distant metastasis and lethality of invasive breast carcinoma. Overexpressing circNR3C2 in vitro and in vivo leads to a crucial enhancement of the tumor-suppressive effects of HRD1 through sponging miR-513a-3p. Conclusions Collectively, we elucidated a bona fide circNR3C2/miR-513a-3p/HRD1/Vimentin axis that negatively regulates the metastasis of TNBC, suggesting that circNR3C2 and HRD1 can act as potential prognostic biomarkers. Our study may facilitate the development of therapeutic agents targeting circNR3C2 and HRD1 for patients with aggressive breast cancer.

Significance of the vimentin expression in triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1056-1056 ◽  
Author(s):  
Nami Yamashita ◽  
Eriko Tokunaga ◽  
Hiroyuki Kitao ◽  
Kimihiro Tanaka ◽  
Kenji Taketani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Ductal Carcinoma ◽  
Growth Factor Receptor ◽  
Cancer Cell Line ◽  
Japanese Patients ◽  
Vimentin Expression ◽  
Mesenchymal Transition

1056 Background: Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The treatment of patients with TNBC has been challenging due to the absence of these molecular targets and the heterogeneity of the disease. Therefore a better understanding of the molecular and histopathological features of TNBC and its heterogeniety is important for the development of a new therapeutic strategy and to improve the prognosis of TNBC. Recent studies suggest that there are links between TNBC and the epithelial-mesenchymal transition (EMT). To identify prognostic biomarkers and novel therapeutic targets, vimentin one of the most major factors associated with EMT was investigated in TNBC. Methods: Sporadic invasive ductal carcinoma specimens were obtained from 659 Japanese patients, and 90 (14%) cases were diagnosed as TNBC. The vimentin mRNA and protein expression levels were evaluated by quantitative RT-PCR and immunohistochemistry. Results: The mRNA expression of vimentin was significantly upregulated in the basal type breast cancer cell line. Immunohistochemically, the vimentin expression was significantly higher (p=0.0042) in TNBC compared to the other subtypes. Vimentin expression was associated with a younger age (p=0.016), high nuclear grade (p=0.023) and high Ki67 expression (p<0.0001), and a poorer prognosis in terms of both the recurrence-free survival (RFS) (p=0.0058) and overall survival (OS) (p=0.013) in TNBC patients. A multivariate analysis showed that vimentin expression was an independent prognostic factor for the RFS (p=0.043). Vimentin expression was also associated with a significantly shorter RFS (p=0.021) and OS (p=0.017) in patients with basal-like breast cancer (BLBC). Conclusions: The elevated expression of vimentin contributes to the aggressive phenotype and poor prognosis in TNBC. Vimentin expression might be useful as a biomarker for the prognosis of TNBC.

Suberoylanilide hydroxamic acid (SAHA) promotes the epithelial mesenchymal transition of triple negative breast cancer cells via HDAC8/FOXA1 signals

2016 ◽  
Vol 397 (1) ◽  
pp. 75-83 ◽  
Author(s):  
Shao Wu ◽  
Zhi Luo ◽  
Peng-Jiu Yu ◽  
Hui Xie ◽  
Yu-Wen He
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Histone Deacetylases ◽  
Hydroxamic Acid ◽  
Triple Negative ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Cancer Agent

Abstract Inhibitor of histone deacetylases (HDACIs) have great therapeutic value for triple negative breast cancer (TNBC) patients. Interestingly, our present study reveals that suberoyl anilide hydroxamic acid (SAHA), one of the most advanced pan-HDAC inhibitor, can obviously promote in vitro motility of MDA-MB-231 and BT-549 cells via induction of epithelial-mesenchymal transition (EMT). SAHA treatment significantly down-regulates the expression of epithelial markers E-cadherin (E-Cad) while up-regulates the mesenchymal markers N-cadherin (N-Cad), vimentin (Vim) and fibronectin (FN). However, SAHA has no effect on the expression and nuclear translocation of EMT related transcription factors including Snail, Slug, Twist and ZEB. While SAHA treatment down-regulates the protein and mRNA expression of FOXA1 and then decreases its nuclear translocation. Over-expression of FOXA1 markedly attenuates SAHA induced EMT of TNBC cells. Further, silence of HDAC8, while not HDAC6, alleviates the down-regulation of FOXA1 and up-regulation of N-Cad and Vim in MDA-MB-231 cells treated with SAHA. Collectively, our present study reveals that SAHA can promote EMT of TNBC cells via HDAC8/FOXA1 signals, which suggests that more attention should be paid when SAHA is used as anti-cancer agent for cancer treatment.

scholarly journals Nonphosphorylatable PEA15 mutant inhibits epithelial-mesenchymal transition in triple-negative breast cancer partly through the regulation of IL-8 expression

2021 ◽  
Author(s):  
Jihyun Park ◽  
Moises J. Tacam ◽  
Gaurav Chauhan ◽  
Evan N. Cohen ◽  
Maria Gagliardi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Lung Metastasis ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Subtype ◽  
Partial Result ◽  
Mesenchymal Transition

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks targeted therapies. Patients with TNBC have a very poor prognosis because the disease often metastasizes. New treatment approaches addressing drivers of metastasis and tumor growth are crucial to improving patient outcomes. Developing targeted gene therapy is thus a high priority for TNBC patients. PEA15 (phosphoprotein enriched in astrocytes, 15 kDa) is known to bind to ERK, preventing ERK from being translocated to the nucleus and hence blocking its activity. The biological function of PEA15 is tightly regulated by its phosphorylation at Ser104 and Ser116. However, the function and impact of phosphorylation status of PEA15 in the regulation of TNBC metastasis and in epithelial-to-mesenchymal transition (EMT) are not well understood. Methods We established stable cell lines overexpressing nonphosphorylatable (PEA15-AA) and phospho-mimetic (PEA15-DD) mutants. To dissect specific cellular mechanisms regulated by PEA15 phosphorylation status, we performed RT-PCR immune and metastasis arrays. In vivo mouse models were used to determine the effects of PEA15 phosphorylation on tumor growth and metastasis. Results We found that the nonphosphorylatable mutant PEA15-AA prevented formation of mammospheres and expression of EMT markers in vitro and decreased tumor growth and lung metastasis in in vivo experiments when compared to control, PEA15-WT and phosphomimetic PEA15-DD. However, phosphomimetic mutant PEA15-DD promoted migration, mesenchymal marker expression, tumorigenesis, and lung metastasis in the mouse model. PEA15-AA-mediated inhibition of breast cancer cell migratory capacity and tumorigenesis was the partial result of decreased expression of interleukin-8 (IL-8). Further, we identified that expression of IL-8 was possibly mediated through one of the ERK downstream molecules, Ets-1. Conclusions Our results show that PEA15 phosphorylation status serves as an important regulator for PEA15’s dual role as an oncogene or tumor suppressor and support the potential of PEA15-AA as a therapeutic strategy for treatment of TNBC.

scholarly journals Inhibition of Vasculogenic Mimicry and Angiogenesis by an Anti-EGFR IgG1-Human Endostatin-P125A Fusion Protein Reduces Triple Negative Breast Cancer Metastases

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2904
Author(s):  
Seung-Uon Shin ◽  
Hyun-Mi Cho ◽  
Rathin Das ◽  
Hava Gil-Henn ◽  
Sundaram Ramakrishnan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Fusion Protein ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Umbilical Vein ◽  
Vasculogenic Mimicry

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited therapeutic options. Metastasis is the major cause of TNBC mortality. Angiogenesis facilitates TNBC metastases. Many TNBCs also form vascular channels lined by tumor cells rather than endothelial cells, known as ‘vasculogenic mimicry’ (VM). VM has been linked to metastatic TNBC behavior and resistance to anti-angiogenic agents. Epidermal growth factor receptor (EGFR) is frequently expressed on TNBC, but anti-EGFR antibodies have limited efficacy. We synthesized an anti-EGFR antibody–endostatin fusion protein, αEGFR IgG1-huEndo-P125A (αEGFR-E-P125A), designed to deliver a mutant endostatin, huEndo-P125A (E-P125A), to EGFR expressing tumors, and tested its effects on angiogenesis, TNBC VM, and motility in vitro, and on the growth and metastasis of two independent human TNBC xenograft models in vivo. αEGFR-E-P125A completely inhibited the ability of human umbilical vein endothelial cells to form capillary-like structures (CLS) and of TNBC cells to engage in VM and form tubes in vitro. αEGFR-E-P125A treatment reduced endothelial and TNBC motility in vitro more effectively than E-P125A or cetuximab, delivered alone or in combination. Treatment of TNBC with αEGFR-E-P125A was associated with a reduction in cytoplasmic and nuclear β-catenin and reduced phosphorylation of vimentin. αEGFR-E-P125A treatment of TNBC xenografts in vivo inhibited angiogenesis and VM, reduced primary tumor growth and lung metastasis of orthotopically implanted MDA-MB-468 TNBC cells, and markedly decreased lung metastases following intravenous injection of MDA-MB-231-4175 lung-tropic TNBC cells. Combined inhibition of angiogenesis, VM, and TNBC motility mediated by αEGFR-E-P125A is a promising strategy for the prevention of TNBC metastases.

scholarly journals XJP Inhibits Apoptosis, Invasion, EMT, and Wnt/Β-Catenin Pathway in Triple-Negative Breast Cancer

2021 ◽  
Author(s):  
Dandan Feng ◽  
Hongzhi Chen ◽  
Guangxi Shi ◽  
Mengdi Zhang ◽  
Hongyi Liang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Triple Negative Breast Cancer ◽  
Molecular Mechanisms ◽  
Triple Negative ◽  
Epithelial Mesenchymal Transition ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Abstract Background: Triple-negative breast cancer (TNBC) progresses at a rapid pace. Chemotherapy is a major clinical application. However, resistance and metastases are key barriers to chemotherapy. Xiaojin pills (XJP) have been used clinically for treating TNBC for decades. However, the potential molecular mechanisms of the effect of XJP on breast cancer is still not understood.Methods: The cell viability was analyzed using Cell Counting Kit-8 (CCK-8). Flow cytometry was used to detect apoptosis, and the migration and invasion abilities of TNBC were assessed using Transwell assay. For molecular mechanisms, the protein expression levels were determined by Western blot analysis. The expression of β-catenin in the Wnt/β-serial protein (β-catenin) pathway was detected with immunofluorescence (IF).Results: XJP inhibited the viability and proliferation of the TNBC cell line in vitro. Flow cytometry analysis showed that apoptosis increased in both MDA-MB-231 and MDA-MB-468 cells induced by XJP. The expression of the proteins associated with invasion, for example, matrix metalloproteinase (MMP) and MMP9, was reduced. Among epithelial–mesenchymal transition markers, E-cadherin was upregulated and N-cadherin was downregulated. The apoptosis-related proteins caspase-8, caspase-3, caspase-9, and Parp were all upregulated. Additionally, XJP effectively suppressed the expression of β-catenin, which belonged to the Wnt/β-catenin pathway.Conclusions: These results suggested that XJP suppressed the progression of TNBC cells by suppressing apoptosis, invasion, EMT, and Wnt/β-catenin pathway.

scholarly journals P01.07 Depletion of CD206high tumour-associated macrophages using a nanoconjugate limits tumour burden & dissemination in metastatic triple negative breast cancer in mice

2021 ◽  
Vol 9 (Suppl 1) ◽  
pp. A6-A7
Author(s):  
A Lepland ◽  
A Malfanti ◽  
U Haljasorg ◽  
S Dordevic ◽  
L Salumäe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Lung Metastases ◽  
Bodyweight Loss ◽  
List Type ◽  
M2 Macrophages ◽  
Polymer Backbone

BackgroundAnti-inflammatory (M2) tumour-associated macrophages (TAMs) exert protumoural roles through angiogenesis, immunosuppression and resistance to therapies.1 M2 TAMs express the mannose receptor, CD206,2 excellent marker for targeted therapies. We have previously identified a peptide called mUNO2 that specifically binds to CD206 on M2 TAMs. Aiming to dissect the role of CD206high M2 TAMs in the tumour progression and immunosuppression, we depleted them using an mUNO and doxorubicin (Adriamycin®)-containing polymer-drug nanoconjugate (St-PGA-DOX-mUNO, ‘OximUNO’) where the polymer backbone is branched polyglutamic acid (St-PGA).3Materials and MethodsWe compared OximUNO with free DOX and the untargeted nanoconjugate St-PGA-DOX. To study the in vitro cytotoxicity of the nanoconjugates, we used M2 and M1 skewed macrophages derived from human blood buffy coat. To study the in vivo homing of nanoconjugates we used an orthotopic triple negative breast cancer (TNBC, 4T1 cells) model and a TNBC experimental metastases model in immunocompetent mice. For in vivo therapeutic efficacy studies, we used orthotopic and experimental metastases models of TNBC, and administered the compounds intraperitoneally (i.p.).ResultsIn vitro, OximUNO showed 39% higher toxicity to the primary human M2 macrophages than St-PGA-DOX, and 31% lower toxicity to the M1 macrophages than St-PGA-DOX. In vivo, OximUNO showed no change in creatinine or alanine aminotransferase values, indicating no toxic effects to the kidneys or liver. Compared to control St-PGA, i.p.-administered St-PGA-mUNO, showed improved homing to M2 TAMs in both orthotopic and experimental metastases models with low accumulation in the liver. In the orthotopic treatment study, only OximUNO significantly reduced the tumour volume and showed 56% and 38% less lung metastases than DOX and St-PGA-DOX, respectively. Additionally, DOX and St-PGA-DOX produced a significant bodyweight loss whereas OximUNO did not. Importantly, OximUNO treatment resulted in 2-5-fold increase in the ratio of CD8+/FOXP3+ expression, suggesting a shift in the immune landscape towards an immunostimulatory profile. In the experimental metastases model, OximUNO monotherapy resulted in the highest reduction of lung metastases, and this effect correlated with a significant reduction in CD206high M2 TAMs; whereas no significant effect on M2 TAMs population was observed with DOX or untargeted nanoconjugate.ConclusionsOur data suggests that the elimination of CD206high M2 TAMs with OximUNO suppresses spontaneous and experimental metastases in safe manner, shifts immune landscape towards immunostimulatory and could therefore be a potential treatment option for TNBC patients.ReferencesHughes R, Qian B-Z, Rowan C, Muthana M, Keklikoglou I, Olson OC, et al. Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Res 2015;75(17):3479–91.Scodeller P, Simón-Gracia L, Kopanchuk S, Tobi A, Kilk K, Säälik P, et al. Precision targeting of tumor macrophages with a CD206 binding peptide. Sci Rep 2017;7(1):14655.Duro-Castano A, Nebot VJ, Niño-Pariente A, Armiñán A, Arroyo-Crespo JJ, Paul A, et al. Capturing ‘extraordinary’ soft-assembled charge-like polypeptides as a strategy for nanocarrier design. Adv Mater 2017;29(39):1702888.Disclosure InformationA. Lepland: None. A. Malfanti: None. U. Haljasorg: None. S. Dordevic: None. L. Salumäe: None. P. Peterson: None. T. Teesalu: None. M.J. Vicent: None. P. Scodeller: None.

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