Background: Tumor-associated macrophages (TAMs) in the tumor microenvironment influence tumor initiation, invasion and metastasis. Several studies have shown that Wnt5a is mainly expressed in the tumor stroma, especially in TAMs. However, whether Wnt5a regulates the polarization and biological function of TAMs in colorectal cancer (CRC) is incompletely understood. Methods: Immunofluorescence staining was performed to detect CD68 and Wnt5a expression in colorectal tissues from patients (63 CRC specimens VS 20 normal tissues). RT-qPCR, flow cytometry, ELISA and inhibitors were carried out to explore the role of Wnt5a in the polarization of TAMs. Clone formation and transwell assays were performed to determine the effects of Wnt5a–treated macrophages on tumor proliferation, migration and invasion in vitro. Finally, a xenograft model was applied to confirm the effects of Wnt5a⁺ TAMs on CRC tumorigenesis. Results: We found that high Wnt5a⁺CD68⁺/CD68⁺ TAMs ratio was significantly associated with poor prognosis in CRC patients and Wnt5a⁺ TAM was an M2-like TAM subtype. Subsequently, we found that Wnt5a induced macrophages to secrete IL-10, which then acted as an autocrine cytokine to induce M2 polarization of these macrophages. IL-10 neutralizing antibody completely reversed the pro-M2 effect of Wnt5a. Mechanistically, the CaKMII-ERK1/2-STAT3 pathway was required for Wnt5a-mediated IL-10 expression in macrophages. Furthermore, Wnt5a-induced M2 macrophages promoted CRC cells proliferation, migration and invasion; knockdown of Wnt5a in TAMs significantly impaired the pro-tumor functions of TAMs. Conclusions: Our data indicate that Wnt5a could induce M2 polarization of TAMs by regulating CaKMII-ERK1/2-STAT3 pathway–mediated IL-10 secretion, ultimately promoting tumor growth and metastasis of CRC.

Background: Tumor-associated macrophages (TAMs) in the tumor microenvironment influence tumor initiation, invasion and metastasis. Several studies have shown that Wnt5a is mainly expressed in the tumor stroma, especially in TAMs. However, whether Wnt5a regulates the polarization and biological function of TAMs in colorectal cancer (CRC) is incompletely understood. Methods: Immunofluorescence staining was performed to detect CD68 and Wnt5a expression in colorectal tissues from patients (63 CRC specimens VS 20 normal tissues). RT-qPCR, flow cytometry, ELISA and inhibitors were carried out to explore the role of Wnt5a in the polarization of TAMs. Clone formation and transwell assays were performed to determine the effects of Wnt5a–treated macrophages on tumor proliferation, migration and invasion in vitro. Finally, a xenograft model was applied to confirm the effects of Wnt5a+ TAMs on CRC tumorigenesis. Results: We found that high Wnt5a+CD68+/CD68+ TAMs ratio was significantly associated with poor prognosis in CRC patients and Wnt5a+ TAM was an M2-like TAM subtype. Subsequently, we found that Wnt5a induced macrophages to secrete IL-10, which then acted as an autocrine cytokine to induce M2 polarization of these macrophages. IL-10 neutralizing antibody completely reversed the pro-M2 effect of Wnt5a. Mechanistically, the CaKMII-ERK1/2-STAT3 pathway was required for Wnt5a-mediated IL-10 expression in macrophages. Furthermore, Wnt5a-induced M2 macrophages promoted CRC cells proliferation, migration and invasion; knockdown of Wnt5a in TAMs significantly impaired the pro-tumor functions of TAMs. Conclusions: Our data indicate that Wnt5a could induce M2 polarization of TAMs by regulating CaKMII-ERK1/2-STAT3 pathway–mediated IL-10 secretion, ultimately promoting tumor growth and metastasis of CRC.

Background: It has been demonstrated that circular RNA (circRNAs) plays a critical role in various cancers. While the potential molecular mechanism of circRNAs in the progression of colorectal cancer (CRC) remains uncertain. Methods: Differentially expressed circRNAs were identified by RNA sequencing. RT-qPCR detected the expression of circ_0009092, miR-665, and NLK in CRC tissues and cells. Functions of circ_0009092 on tumor cell proliferation, migration, and invasion were investigated by a series of in vitro assays. The underlying mechanism of circ_0009092 was explored by bioinformatics analysis, RNA immunoprecipitation (RIP) and luciferase assays. A co-culture assay in vitro was performed to detect the affection of circ_0009092 on macrophage recruitment in the tumor microenvironment (TME). A xenograft mouse model was used to explore the effect of circ_0009092 on tumor growth. Results: Circ_0009092 was downregulated in CRC and predicted a good prognosis. Overexpression of circ_0009092 reduced tumor cell EMT, proliferation, migration, and invasion in vitro and in vivo. Mechanistically, circ_0009092 elevated the NLK expression via sponging miR-665 and suppressed the Wnt/β-catenin signaling pathway. EIF4EA3 induced circ_0009092 expression in CRC cells. In addition, NLK regulates phosphorylation and O-GlcNAcylation of STAT3 by binding to STAT3, thereby inhibiting CCL2 expression, in which it inhibits macrophage recruitment in the tumor microenvironment (TME). Conclusion: EIF4A3 suppressed circ_0009092 biogenesis, which inhibits CRC progression by sponging miR-665 to downregulate NLK. Circ_0009092/miR-665/NLK suppressed tumor EMT, proliferation, migration, and invasion by acting on the Wnt/β-catenin signaling pathway. NLK directly interacted with STAT3 and decreased the CCL2 expression, inhibiting the recruitment of tumor-associated macrophages (TAMs) in the TME. Our study provided novel insights into the roles of circ_0009092 as a novel promising prognostic and therapeutic target in CRC.

Rationale: Malignant central airway obstruction (MCAO) represents a life-threatening oncologic emergency that can lead to rapid respiratory decompensation and death. Traditional management with mechanical ventilation may be inadequate or risky when severe airway narrowing or complete obstruction exists. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) offers an alternative method of gas exchange that can support patients during high-risk airway interventions. This article presents 3 cases and reviews existing literature to evaluate the role of VV-ECMO as a bridge therapy for airway procedures in patients with MCAO. Patient concerns: All 3 patients presented with symptomatic airway stenosis secondary to malignant pulmonary or metastatic tumors, and conventional tracheal intubation failed to maintain adequate oxygenation and ventilation, necessitating urgent advanced respiratory support. Diagnoses: All 3 patients were diagnosed with respiratory failure secondary to bronchial obstruction caused by primary or secondary malignant lung tumors. Interventions: All patients were initiated on heparin-free VV-ECMO to establish stable extracorporeal gas exchange, followed by definitive interventional therapy via flexible bronchoscopy, including tumor debulking and/or airway stenting. Outcomes: Immediate improvement in oxygenation was achieved in all 3 patients following ECMO-supported intervention. Lessons: VV-ECMO serves as a viable bridge to definitive airway interventions in carefully selected patients with MCAO. Anticoagulation management requires careful balance, with a no-heparin protocol appearing safe for brief ECMO runs. Multidisciplinary collaboration is essential for optimal outcomes in these complex cases.

Background Epithelial-mesenchymal transition (EMT) is involved in the interaction between cancer cells and tumor-associated macrophages (TAMs) in the tumor microenvironment (TME), which intimately affects tumorigenicity and metastasis. However, the potential mechanisms of EMT and the understanding of how EMT-programmed cancer cells affect TAMs recruitment and polarization remain further investigation. Methods The expression of LINC01671, miR-141-3p, miR-186-5p, and YY1 in CRC tissues and cells were detected by RT-qPCR. Functions of LINC01671 on cancer cell proliferation, migration, invasion and EMT were examined by a series of in vitro assays. The underlying mechanism of LINC01671 was investigated by bioinformatics analysis, RNA pull-down, luciferase reporter, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation assays. A co-culture assay in vitro was used to detect the effect of LINC01671 on macrophage recruitment and polarization in TME. A xenograft mouse model was performed to explore the role of LINC01671 on tumorigenicity and TAM polarization. Results LncRNA LINC01671 was significantly overexpressed in colorectal cancer (CRC) tissues, and high LINC01671 level was positively correlated with poor prognosis in CRC patients. Elevated LINC01671 promoted CRC cells proliferation, migration, invasion and EMT in vitro as well as tumor growth and metastasis in vivo. Mechanistically, LINC01671 served as a sponge for miR-141-3p and miR-186-5p to facilitate YY1 expression, which in turn transcriptionally activated LINC01671 expression. Moreover, LINC01671/YY1 modulated CCL2 secretion during CRC cells EMT and subsequently favored TAMs infiltration and M2-like polarization in TME. Conclusion Our data demonstrate that LINC01671, identified as an oncogene, may play a crucial role in regulating YY1-mediated cancer cell EMT, thereby affecting CCL2-related M2-like TAM recruitment in CRC.