التفاصيل البيبلوغرافية
| العنوان: |
Macrophage-Induced Carboxypeptidase A4 Promotes the Progression of Anaplastic Thyroid Cancer. |
| المؤلفون: |
Choi YS; Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Jeon MJ; Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Doolittle WKL; Department of Medicine, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA., Song DE; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim K; Departments of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim WB; Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea., Kim WG; Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. |
| المصدر: |
Thyroid : official journal of the American Thyroid Association [Thyroid] 2024 May 13. Date of Electronic Publication: 2024 May 13. |
| Publication Model: |
Ahead of Print |
| نوع المنشور: |
Journal Article |
| اللغة: |
English |
| بيانات الدورية: |
Publisher: Mary Ann Liebert Publishers Country of Publication: United States NLM ID: 9104317 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-9077 (Electronic) Linking ISSN: 10507256 NLM ISO Abbreviation: Thyroid Subsets: MEDLINE |
| أسماء مطبوعة: |
Original Publication: New York, NY : Mary Ann Liebert Publishers, |
| مستخلص: |
Background: The density of tumor-associated macrophages in the tumor microenvironment of anaplastic thyroid cancer (ATC) is associated with poor prognosis. However, the crosstalk between macrophages and ATC cells is poorly understood. This study aimed to examine the impact of macrophages on cancer cell phenotypes. We found a new mediator between M2 macrophages and ATC cells through proteomics analysis. Methods: The role of macrophages in proliferation, migration, and invasion of ATC cells was evaluated using coculture assay and conditioned medium (CM). Secretory factors in the CM from single or coculture were identified using liquid chromatography-tandem mass spectrometry proteomics analysis. We evaluated the role of the secretory factor in proliferation, migration, and invasion of cancer cells. In vivo xenograft model was used to evaluate the effect of the factor. Results: M2 macrophages significantly increased the proliferation, migration, and invasion of ATC cells, whereas M1 macrophages decreased the proliferation, migration, and invasion of ATC cells. Based on proteomic analysis of CM, we identify carboxypeptidase A4 (CPA4) as a mediator of the crosstalk between macrophages and ATC cells. CPA4 was only detected in the coculture media of M2 macrophage/8505C, and its expression in cancer cells increased by M2 macrophage. The expression of CPA4 protein was significantly higher in human thyroid cancers, particularly in ATCs, than normal and benign tissues. A bioinformatics analysis of public data revealed that CPA4 expression was associated with poor prognosis and dedifferentiation of thyroid cancer. Knockdown of CPA4 suppressed proliferation, colony formation, migration, and invasion of ATC cells, consistent with the decrease of STAT3, ERK, and AKT/mTOR phosphorylation and epithelial-mesenchymal transition (EMT) marker expression. In addition, the increased expression of CPA4 in cancer cells by M2 macrophage stimulation induced the polarization of macrophages to the M2 phenotype, which formed a positive feedback loop. Xenograft tumors did not develop after CPA4 knockdown. Conclusions: Our data suggest that CPA4 stimulates the progression of thyroid cancer by mediating between M2 macrophages and ATC cells. CPA4 can be a new therapeutic target for the treatment of patients with ATC. |
| فهرسة مساهمة: |
Keywords: anaplastic carcinoma; carboxypeptidase; macrophage; microenvironment; thyroid carcinoma |
| تواريخ الأحداث: |
Date Created: 20240426 Latest Revision: 20240513 |
| رمز التحديث: |
20240513 |
| DOI: |
10.1089/thy.2023.0427 |
| PMID: |
38666696 |
| قاعدة البيانات: |
MEDLINE |
