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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. [ABSTRACT FROM AUTHOR]

Background: Granulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth. Case presentation: A 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/μL to 8490/μL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45. Conclusions: G-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods. [ABSTRACT FROM AUTHOR]