CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation

Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by...

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Vydané v:	Immunity (Cambridge, Mass.) Ročník 44; číslo 2; s. 303 - 315
Hlavní autori:	Kumar, Vinit, Cheng, Pingyan, Condamine, Thomas, Mony, Sridevi, Languino, Lucia R, McCaffrey, Judith C, Hockstein, Neil, Guarino, Michael, Masters, Gregory, Penman, Emily, Denstman, Fred, Xu, Xiaowei, Altieri, Dario C, Du, Hong, Yan, Cong, Gabrilovich, Dmitry I
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 16.02.2016
Predmet:	Animals Cell Differentiation Cell Movement Cells, Cultured Dimerization Female Hypoxia - immunology Leukocyte Common Antigens - genetics Leukocyte Common Antigens - metabolism Macrophages - immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Myeloid Cells - immunology Phosphoric Monoester Hydrolases - genetics Phosphoric Monoester Hydrolases - metabolism Sialic Acids - metabolism STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism Tumor Microenvironment
ISSN:	1097-4180
On-line prístup:	Zistit podrobnosti o prístupe
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Abstract	Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.
AbstractList	Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing to tumor progression and metastasis. We demonstrated that differentiation of TAMs in tumor site from monocytic precursors was controlled by downregulation of the activity of the transcription factor STAT3. Decreased STAT3 activity was caused by hypoxia and affected all myeloid cells but was not observed in tumor cells. Upregulation of CD45 tyrosine phosphatase activity in MDSCs exposed to hypoxia in tumor site was responsible for downregulation of STAT3. This effect was mediated by the disruption of CD45 protein dimerization regulated by sialic acid. Thus, STAT3 has a unique function in the tumor environment in controlling the differentiation of MDSC into TAM, and its regulatory pathway could be a potential target for therapy.
Author	Du, Hong Condamine, Thomas Mony, Sridevi Languino, Lucia R Cheng, Pingyan Gabrilovich, Dmitry I Penman, Emily Xu, Xiaowei Guarino, Michael Kumar, Vinit McCaffrey, Judith C Denstman, Fred Altieri, Dario C Hockstein, Neil Yan, Cong Masters, Gregory
Author_xml	– sequence: 1 givenname: Vinit surname: Kumar fullname: Kumar, Vinit organization: The Wistar Institute, Philadelphia, PA 19104, USA – sequence: 2 givenname: Pingyan surname: Cheng fullname: Cheng, Pingyan organization: H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA – sequence: 3 givenname: Thomas surname: Condamine fullname: Condamine, Thomas organization: The Wistar Institute, Philadelphia, PA 19104, USA – sequence: 4 givenname: Sridevi surname: Mony fullname: Mony, Sridevi organization: The Wistar Institute, Philadelphia, PA 19104, USA – sequence: 5 givenname: Lucia R surname: Languino fullname: Languino, Lucia R organization: Thomas Jefferson University, Philadelphia, PA 19110, USA – sequence: 6 givenname: Judith C surname: McCaffrey fullname: McCaffrey, Judith C organization: H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA – sequence: 7 givenname: Neil surname: Hockstein fullname: Hockstein, Neil organization: Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA – sequence: 8 givenname: Michael surname: Guarino fullname: Guarino, Michael organization: Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA – sequence: 9 givenname: Gregory surname: Masters fullname: Masters, Gregory organization: Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA – sequence: 10 givenname: Emily surname: Penman fullname: Penman, Emily organization: Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA – sequence: 11 givenname: Fred surname: Denstman fullname: Denstman, Fred organization: Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA – sequence: 12 givenname: Xiaowei surname: Xu fullname: Xu, Xiaowei organization: University of Pennsylvania, Philadelphia, PA 19104, USA – sequence: 13 givenname: Dario C surname: Altieri fullname: Altieri, Dario C organization: The Wistar Institute, Philadelphia, PA 19104, USA – sequence: 14 givenname: Hong surname: Du fullname: Du, Hong organization: Indiana University School of Medicine, Indianapolis, IN 46202, USA – sequence: 15 givenname: Cong surname: Yan fullname: Yan, Cong organization: Indiana University School of Medicine, Indianapolis, IN 46202, USA – sequence: 16 givenname: Dmitry I surname: Gabrilovich fullname: Gabrilovich, Dmitry I email: dgabrilovich@wistar.org organization: The Wistar Institute, Philadelphia, PA 19104, USA. Electronic address: dgabrilovich@wistar.org
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/26885857$$D View this record in MEDLINE/PubMed
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Snippet	Recruitment of monocytic myeloid-derived suppressor cells (MDSCs) and differentiation of tumor-associated macrophages (TAMs) are the major factors contributing...
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SubjectTerms	Animals Cell Differentiation Cell Movement Cells, Cultured Dimerization Female Hypoxia - immunology Leukocyte Common Antigens - genetics Leukocyte Common Antigens - metabolism Macrophages - immunology Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Myeloid Cells - immunology Phosphoric Monoester Hydrolases - genetics Phosphoric Monoester Hydrolases - metabolism Sialic Acids - metabolism STAT3 Transcription Factor - genetics STAT3 Transcription Factor - metabolism Tumor Microenvironment
Title	CD45 Phosphatase Inhibits STAT3 Transcription Factor Activity in Myeloid Cells and Promotes Tumor-Associated Macrophage Differentiation
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