scholarly journals Tumor-Derived Exosomal Protein Tyrosine Phosphatase Receptor Type O Polarizes Macrophage to Suppress Breast Tumor Cell Invasion and Migration

2021 ◽  
Vol 9 ◽  
Author(s):  
Hongmei Dong ◽  
Chaoyu Xie ◽  
Yuchen Jiang ◽  
Kai Li ◽  
Yusheng Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cell ◽  
Cell Invasion ◽  
Protein Tyrosine Phosphatase ◽  
Macrophage Polarization ◽  
Tyrosine Phosphatase ◽  
Receptor Type ◽  
Protein Tyrosine ◽  
Invasion And Migration ◽  
And Migration

Tumor-derived exosomes, containing multiple nucleic acids and proteins, have been implicated to participate in the interaction between tumor cells and microenvironment. However, the functional involvement of phosphatases in tumor-derived exosomes is not fully understood. We and others previously demonstrated that protein tyrosine phosphatase receptor type O (PTPRO) acts as a tumor suppressor in multiple cancer types. In addition, its role in tumor immune microenvironment remains elusive. Bioinformatical analyses revealed that PTPRO was closely associated with immune infiltration, and positively correlated to M1-like macrophages, but negatively correlated to M2-like macrophages in breast cancer tissues. Co-cultured with PTPRO-overexpressing breast cancer cells increased the proportion of M1-like tumor-associated macrophages (TAMs) while decreased that of M2-like TAMs. Further, we observed that tumor-derived exosomal PTPRO induced M1-like macrophage polarization, and regulated the corresponding functional phenotypes. Moreover, tumor cell-derived exosomal PTPRO inhibited breast cancer cell invasion and migration, and inactivated STAT signaling in macrophages. Our data suggested that exosomal PTPRO inhibited breast cancer invasion and migration by modulating macrophage polarization. Anti-tumoral effect of exosomal PTPRO was mediated by inactivating STAT family in macrophages. These findings highlight a novel mechanism of tumor invasion regulated by tumor-derived exosomal tyrosine phosphatase, which is of translational potential for the therapeutic strategy against breast cancer.

IL-6 influences PD-L1 expression in monocytes and macrophages by effecting protein tyrosine phosphatase receptor type O expression in-human breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15570-e15570
Author(s):  
Lin Chen ◽  
Jinhai Tang
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Protein Tyrosine Phosphatase ◽  
Human Breast Cancer ◽  
Tyrosine Phosphatase ◽  
Receptor Type ◽  
Human Breast ◽  
Protein Tyrosine ◽  
Monocytes And Macrophages

e15570 Background: We have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human breast cancer (BC). Methods: The expression and correlation of all the indices were explored in monocytes and tumor infiltrating macrophages within both human and mice BC. The mechanic regulations were studied by using both in vitro and in vivo studies. Results: We found a significant decrease in PTPRO in BC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in BC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with BC and were associated with increased T cell exhaustion (Tim3+ T cells). A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25-3p axis. Monocytes and TAMs showed significantly increased miR-25-3p expression, which could target the 3' untranslated region of PTPRO. The miR-25-3p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in BC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25-3p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25-3p–modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1–induced immunosuppression in breast tumor model. Conclusions: Increased serum IL-6 downregulated PTPRO expression in BC monocytes and macrophages by activating STAT3/c-MYC/miR-25-3p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.

scholarly journals Loss of protein tyrosine phosphatase, non-receptor type 2 is associated with activation of AKT and tamoxifen resistance in breast cancer

2015 ◽  
Vol 153 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Elin Karlsson ◽  
Cynthia Veenstra ◽  
Shad Emin ◽  
Chhanda Dutta ◽  
Gizeh Pérez-Tenorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Tamoxifen Resistance ◽  
Receptor Type ◽  
Protein Tyrosine

scholarly journals The protein tyrosine phosphatase receptor type H, PTPRH, is differentially expressed in the primary tumors of breast cancer patients treated with trastuzumab.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Growth Factor Receptor ◽  
Differentially Expressed ◽  
Receptor Type ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Protein Tyrosine ◽  
Pediatric Solid Tumors

Trastuzumab, a monoclonal antibody targeted against the human epidermal growth factor receptor 2 (HER2) is utilized for the treatment of human breast cancer (1, 2), but a complete understanding of how tumor signal transduction is modulated by trastuzumab treatment is lacking. By mining published and public microarray and gene expression data (3, 4) from the primary tumors of patients treated with trastuzumab, we found that the protein tyrosine phosphatase receptor type H, encoded by PTPRH, was among the genes most differentially expressed in the primary tumors of patients treated with trastuzumab, and expressed at lower levels in the tumors of patients treated with trastuzumab. Thus, the use of trastuzumab in patients with breast cancer is associated with decreased primary tumors expression of a protein tyrosine phosphatase whose deficiency in pediatric solid tumors defines a risk-phenotype (5) and whose expression is decreased in colorectal cancer (6).

scholarly journals Protein tyrosine phosphatase receptor-type δ acts as a negative regulator suppressing breast cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (58) ◽  
pp. 98798-98811 ◽  
Author(s):  
Xiaotang Yu ◽  
Fan Zhang ◽  
Jun Mao ◽  
Ying Lu ◽  
Jiazhi Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Receptor Type ◽  
Protein Tyrosine

A Review on Phytopharmaceutical shaving Concomitant Experimental Anti-Diabetic and Anti-Cancer Effects as Potential Sources for Targeted Therapies Against Insulin Mediated Breast Cancer Cell Invasion and Migration

2020 ◽  
Vol 16 ◽  
Author(s):  
Vibhavana Singh ◽  
Rakesh Reddy ◽  
Antarip Sinha ◽  
Venkatesh Marturi ◽  
Shravani Sripathi Panditharadyula ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Medicinal Plants ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Invasion ◽  
Breast Tumor ◽  
Cancer Cell Invasion ◽  
Invasion And Migration ◽  
Anti Cancer ◽  
And Migration

: Diabetes and breast cancer are pathophysiologically similar and clinically established diseases that co-exist with a wider complex similar molecular signalling and having similar set of risk factors. Insulin plays a pivotal role for invasion and migration of breast cancer cells. Several ethnopharmacological evidences light the concomitant anti-diabetic and anti-cancer activity of medicinal plant and phytochemicals against breast tumor of patients with diabetes. This present article reviewed the findings on medicinal plants and phytochemicals with concomitant anti-diabetic and anti-cancer effects reported in scientific literature to facilitate the development of dual-acting therapies against diabetes and breast cancer. The schematic tabular form of published literatures on medicinal plants (63 plants belongs to 45 families) concluded the dynamics of phytochemicals against diabetes and breast tumor that could be explored further for the discovery of therapies for controlling of breast cancer cell invasion and migration in patient with diabetes.

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