AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages
Summary: Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated....
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723010781 |
| _version_ | 1797706860724224000 |
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| author | Chia-Nung Hung Meizhen Chen Daniel T. DeArmond Cheryl H.-L. Chiu Catherine A. Limboy Xi Tan Meena Kusi Chih-Wei Chou Li-Ling Lin Zhao Zhang Chiou-Miin Wang Chun-Liang Chen Kohzoh Mitsuya Pawel A. Osmulski Maria E. Gaczynska Nameer B. Kirma Ratna K. Vadlamudi Don L. Gibbons Steve Warner Andrew J. Brenner Daruka Mahadevan Joel E. Michalek Tim H.-M. Huang Josephine A. Taverna |
| author_facet | Chia-Nung Hung Meizhen Chen Daniel T. DeArmond Cheryl H.-L. Chiu Catherine A. Limboy Xi Tan Meena Kusi Chih-Wei Chou Li-Ling Lin Zhao Zhang Chiou-Miin Wang Chun-Liang Chen Kohzoh Mitsuya Pawel A. Osmulski Maria E. Gaczynska Nameer B. Kirma Ratna K. Vadlamudi Don L. Gibbons Steve Warner Andrew J. Brenner Daruka Mahadevan Joel E. Michalek Tim H.-M. Huang Josephine A. Taverna |
| author_sort | Chia-Nung Hung |
| collection | DOAJ |
| description | Summary: Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting “M2-like” phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to interact with endothelial cells and facilitate formation of primitive vascular networks. We also found that AXL-STAT3 inhibition can impede the recruitment of TAMs in a xenograft mouse model, thereby suppressing tumor growth. These findings suggest the potential application of AXL-STAT3-related markers to quantitatively assess metastatic potential and inform therapeutic strategies in lung cancer. |
| first_indexed | 2024-03-12T05:58:41Z |
| format | Article |
| id | doaj.art-81e2c4bf9d664349a0f9840fc517001b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T05:58:41Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-81e2c4bf9d664349a0f9840fc517001b2023-09-03T04:23:49ZengElsevierCell Reports2211-12472023-09-01429113067AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophagesChia-Nung Hung0Meizhen Chen1Daniel T. DeArmond2Cheryl H.-L. Chiu3Catherine A. Limboy4Xi Tan5Meena Kusi6Chih-Wei Chou7Li-Ling Lin8Zhao Zhang9Chiou-Miin Wang10Chun-Liang Chen11Kohzoh Mitsuya12Pawel A. Osmulski13Maria E. Gaczynska14Nameer B. Kirma15Ratna K. Vadlamudi16Don L. Gibbons17Steve Warner18Andrew J. Brenner19Daruka Mahadevan20Joel E. Michalek21Tim H.-M. Huang22Josephine A. Taverna23Department of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Cardiothoracic Surgery, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Office of Nursing Research & Scholarship, School of Nursing, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USAMays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, TX, USADepartment of Thoracic, Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USASumitomo Pharma Oncology, Inc, Lehi, UT, USAMays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Division of Hematology and Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USAMays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Division of Hematology and Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USADepartment of Population Health Sciences, University of Texas Health Science Center, San Antonio, TX, USADepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Corresponding authorDepartment of Molecular Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health Science Center, San Antonio, TX, USA; Division of Hematology and Oncology, Department of Medicine, University of Texas Health Science Center, San Antonio, TX, USA; Corresponding authorSummary: Tumor-associated macrophages (TAMs) are integral to the development of complex tumor microenvironments (TMEs) and can execute disparate cellular programs in response to extracellular cues. However, upstream signaling processes underpinning this phenotypic plasticity remain to be elucidated. Here, we report that concordant AXL-STAT3 signaling in TAMs is triggered by lung cancer cells or cancer-associated fibroblasts in the cytokine milieu. This paracrine action drives TAM differentiation toward a tumor-promoting “M2-like” phenotype with upregulation of CD163 and putative mesenchymal markers, contributing to TAM heterogeneity and diverse cellular functions. One of the upregulated markers, CD44, mediated by AXL-IL-11-pSTAT3 signaling cascade, enhances macrophage ability to interact with endothelial cells and facilitate formation of primitive vascular networks. We also found that AXL-STAT3 inhibition can impede the recruitment of TAMs in a xenograft mouse model, thereby suppressing tumor growth. These findings suggest the potential application of AXL-STAT3-related markers to quantitatively assess metastatic potential and inform therapeutic strategies in lung cancer.http://www.sciencedirect.com/science/article/pii/S2211124723010781CP: CancerCP: Immunology |
| spellingShingle | Chia-Nung Hung Meizhen Chen Daniel T. DeArmond Cheryl H.-L. Chiu Catherine A. Limboy Xi Tan Meena Kusi Chih-Wei Chou Li-Ling Lin Zhao Zhang Chiou-Miin Wang Chun-Liang Chen Kohzoh Mitsuya Pawel A. Osmulski Maria E. Gaczynska Nameer B. Kirma Ratna K. Vadlamudi Don L. Gibbons Steve Warner Andrew J. Brenner Daruka Mahadevan Joel E. Michalek Tim H.-M. Huang Josephine A. Taverna AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages Cell Reports CP: Cancer CP: Immunology |
| title | AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages |
| title_full | AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages |
| title_fullStr | AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages |
| title_full_unstemmed | AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages |
| title_short | AXL-initiated paracrine activation of pSTAT3 enhances mesenchymal and vasculogenic supportive features of tumor-associated macrophages |
| title_sort | axl initiated paracrine activation of pstat3 enhances mesenchymal and vasculogenic supportive features of tumor associated macrophages |
| topic | CP: Cancer CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723010781 |
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