Secondary perianal Paget’s disease (PPD) is a rare clinical entity resulting from the intraepithelial dissemination of an underlying adenocarcinoma, yet cases involving anal gland adenocarcinoma in situ with generalized pagetoid spread remain exceptionally rare and poorly documented in existing literature. We present the case of a 62-year-old female with a three-year history of persistent perianal pruritus and exudation whose initial physical examinations and systemic imaging (CT, MRI, and colonoscopy) failed to reveal a visible malignancy. Following wide local excision and comprehensive histopathological sampling of the specimen, a microscopic focus of well-differentiated anal gland adenocarcinoma in situ was identified, manifesting with extensive pagetoid spread into the epidermis. Immunohistochemical analysis confirmed the diagnosis through positivity for CK7, CK20, and CDX-2, alongside negative staining for GCDFP-15 and mammaglobin, while p53 expression showed a wild-type pattern and the Ki-67 index reached 70%. This report highlights that secondary PPD must be considered in patients with refractory perianal symptoms even without a detectable mass, emphasizing that rigorous pathological examination and specific IHC markers are paramount for identifying occult primary lesions and ensuring optimal surgical outcomes.

Breast cancer (BC) is one of the leading diseases that severely threaten women’s lives and health worldwide, with chemoresistance remaining a major challenge in its treatment. The tumor microenvironment, particularly cancer-associated fibroblasts (CAFs), plays a critical role in the chemoresistance of tumor cells, but the underlying mechanisms involved still require further exploration. This study aims to investigate the role and potential mechanisms of the positive feedback loop formed by CAF-derived NRG1 and BC cell-derived PDGFC in paclitaxel resistance. To this end, we isolated primary CAFs from BC patients and established co-culture systems with BC cell lines to observe the impact of CAFs on paclitaxel resistance in BC cells. Exogenous NRG1 and the knockdown of NRG1 in CAFs were used to reveal the regulatory role of CAF-derived NRG1 in paclitaxel resistance in BC cells. CCK-8 assay, transmission electron microscopy, MDA and GSH/GSSG content measurements, as well as JC-1 assay, were used to assess ferroptosis levels in BC cells. Additionally, exogenous PDGFC and co-culture systems were used to investigate the effects of tumor cell-derived PDGFC on fibroblasts. Using a BC ectopic xenograft mouse model, we investigated the regulatory role of NRG1 and PDGFC in paclitaxel resistance in vivo. Our results showed that CAF-derived NRG1 significantly promoted paclitaxel resistance and ferroptosis escape in BC cells, while the AKT inhibitor effectively suppressed this effect. Moreover, BC cell-derived PDGFC activated fibroblasts and induced their high expression of NRG1. These findings suggest that CAF-derived NRG1 enhances ferroptosis escape and paclitaxel resistance in BC cells through the AKT/mTOR pathway, while also inducing cancer cells to express high levels of PDGFC. In turn, cancer cell-derived PDGFC promotes fibroblast activation and high NRG1 expression, forming a positive feedback loop between NRG1 and PDGFC. This feedback loop ultimately results in a malignant cycle of paclitaxel resistance in BC.

Tumor recurrence often occurs years after initial treatment, driven by dormant tumor cells that evade detection and therapy. These quiescent cells can persist in primary or metastatic niches and later reawaken under favorable microenvironmental conditions, contributing to cancer relapse. Tumor-associated macrophages (TAMs) have emerged as key regulators in orchestrating this proliferation-dormancy switch. Through secretion of cytokines, extracellular vesicles, and direct cellular interactions, macrophages influence tumor cell fate via multiple signaling pathways, including TGF-β, WNT, and HIPPO. These pathways modulate the expression of cell cycle regulators, such as cyclins and cyclin-dependent kinase inhibitors (CKIs), ultimately governing the transition between proliferation and dormancy. This review synthesizes current findings on the roles of macrophages in initiating and maintaining tumor cell dormancy across various solid tumors. We discuss how distinct macrophage subtypes—defined by developmental origin or polarization state—differentially engage with tumor cells to modulate dormancy-associated signaling cascades. Understanding these spatiotemporal interactions between macrophages and tumor cells offers novel opportunities for therapeutic intervention aimed at preventing relapse by targeting the dormant tumor cell niche.

Uncoupling protein-2 (UCP2) controls the antioxidant response and redox homeostasis in cancer and is considered a potent molecular target for cancer treatment. However, the specific mechanism of UCP2 inhibition and its role in glioblastoma (GBM) have not yet been elucidated. Here, we attempt to identify a UCP2 inhibitor and study the underlying molecular mechanism in GBM. Bioinformatics analysis and immunohistochemistry are used to validate the high expression of UCP2 in GBM and its prognostic significance. Drug intervention and tumor xenograft experiments are conducted to determine the inhibitory effect of genipin, a UCP2 inhibitor, on UCP2. The mitochondrial membrane potential and key ferroptosis genes are examined to determine the occurrence of ferroptosis. High expression of UCP2 in GBM is associated with poor prognosis, and inhibiting UCP2 can alleviate the malignant behavior of GBM tumors. Genipin can downregulate the expression of GPX4 and upregulate the expression of ACSL4 by inhibiting UCP2, leading to ferroptosis and alleviating the malignant behavior of tumors. In summary, UCP2 is a potential therapeutic target for GBM. Genipin, which targets UCP2, effectively inhibits GBM development by inducing ferroptosis in vivo and in vitro. These findings indicate that genipin treatment based on UCP2 targeting has potential therapeutic applications with a clinical perspective for the treatment of GBM patients.

Clear cell (glycogen-rich) urothelial carcinoma is an exceedingly rare variant of invasive urothelial carcinoma, distinguished by the presence of abundant cytoplasmic glycogen, which imparts a clear appearance to the tumor cells under histological examination. In this case report, the diagnosis was established through histopathological evaluation with hematoxylin and eosin (HE) staining, immunohistochemical analysis, and the identification of significant cytoplasmic glycogen accumulation. The patient, an 89-year-old male, was admitted on July 24, 2024, presenting with painless gross hematuria persisting for one week. Abdominal ultrasound and CT urography revealed a soft tissue mass on the right side of the bladder wall, measuring 30 × 30 mm, with a broad base connected to the bladder wall. The mass exhibited significant enhancement on contrast-enhanced scans, raising suspicion for malignancy. Microscopic examination revealed two distinct tumor cell morphologies: the conventional urothelial carcinoma pattern and a clear nest-like morphology, with the latter comprising over 70

Breast cancer (BC) represents one of the most prevalent malignancies in the female population and constitutes a leading cause of cancer-associated mortality among women globally. The emergence of chemoresistance persists as a critical challenge in current breast cancer therapeutic strategies. Malignant tumors are enveloped by a sophisticated assemblage of cellular and non-cellular components that collectively establish the tumor microenvironment (TME). Notably, tumor-associated macrophages (TAMs), being one of the most abundant immune infiltrates within the TME, have been demonstrated to play an instrumental role in the development and progression of chemotherapeutic resistance mechanisms. Recent studies have revealed that TAMs and breast cancer cells engage in complex bidirectional interactions. This crosstalk not only facilitates tumor immune evasion but also promotes chemotherapy resistance in breast cancer through the secretion of various cytokines, chemokines, growth factors, and other bioactive molecules. Therefore, elucidating the underlying mechanisms by which TAMs contribute to chemotherapy resistance is of significant importance. This review summarizes the dynamic and bidirectional regulatory network formed between TAMs and BC. Centering on this network, it comprehensively analyzes the molecular mechanisms by which TAMs regulate chemotherapy resistance in BC, summarizes potential targeted drugs that disrupt molecular interactions between TAMs and BC, and discusses the therapeutic prospects of combining these drugs with chemotherapy and immunotherapy. The findings aim to provide novel insights into potential molecular targets for overcoming chemotherapy resistance and to explore new therapeutic strategies for breast cancer patients.

Studies of cell-to-cell activities in the tumor microenvironment (TME) have identified multiple potential targets for oncotherapy. The interplay between tumor cells and neighboring cancer-associated fibroblasts (CAFs) persists in all stages of tumor progression. In this study, we reveal that exosomes from breast cancer cells can be endocytosed into fibroblasts and transform normal fibroblasts (NFs) into CAFs and that the ability of exosomes from highly metastatic breast cancer cells is greater than that of those from poorly metastatic breast cancer cells. Further investigation reveals that exosomes from highly metastatic breast cancer cells contain much more miR-105-5p than those from poorly metastatic breast cells do and that exosomal miR-105-5p facilitates the transformation of NFs to CAFs. A detailed study reveals that RBMY1A1-dependent sorting of miR-105-5p into fibroblasts and subsequent internalization of miR-105-5p promote the transformation of NFs to CAFs by downregulating LATS2 expression and activating NF-κB signaling, which concurrently facilitates the EMT of breast cancer cells. Thus, our results indicate that exosomal miR-105-5p may be a potential target for novel therapeutic strategies to prevent the coevolution of breast cancer cells and CAFs.

Cancer cells play a pivotal role in immune evasion by activating the programmed cell death protein 1 (PD‑1)/PD‑ligand (L)1 signaling pathway or immune cells within the tumor microenvironment. The ubiquitin‑proteasome system (UPS), the primary pathway for intracellular protein degradation, has been increasingly implicated in mediating tumor immune escape and resistance to anti‑PD‑1/PD‑L1 therapy. Targeting the UPS has demonstrated significant potential in improving the efficacy of tumor immunotherapy. Therefore, a deeper understanding of the molecular mechanisms by which UPS contributes to tumor resistance against PD‑1/PD‑L1 blockade, along with the optimization of UPS‑targeted small‑molecule drug design, holds scientific and clinical significance. In the present review, the role of UPS in tumor immune evasion through the regulation of PD‑1/PD‑L1 ubiquitination was discussed and potential therapeutic agents that may enhance the effectiveness of anti‑PD‑1/PD‑L1 treatment are summarized. These insights provide a theoretical foundation for advancing cancer immunotherapy and developing novel combination strategies.

Stroke poses a threat to the elderly, being the second leading cause of death and the third leading cause of disability worldwide. Ischemic stroke (IS), resulting from arterial occlusion, accounts for ~85% of all strokes. The pathophysiological processes involved in IS are intricate and complex. Currently, tissue plasminogen activator (tPA) is the only Food and Drug Administration‑approved drug for the treatment of IS. However, due to its limited administration window and the risk of symptomatic hemorrhage, tPA is applicable to only ~10% of patients with stroke. Additionally, the reperfusion process associated with thrombolytic therapy can further exacerbate damage to brain tissue. Therefore, a thorough understanding of the molecular mechanisms underlying IS‑induced injury and the identification of potential protective agents is critical for effective IS treatment. Over the past few decades, advances have been made in exploring potential protective drugs for IS. The present review summarizes the specific mechanisms of various forms of programmed cell death (PCD) induced by IS and highlights potential protective drugs targeting different PCD pathways investigated over the last decade. The present review provides a theoretical foundation for basic research and insights for the development of pharmacotherapy for IS.

This study elucidates the mechanisms by which cancer-associated fibroblast (CAF)-derived platelet-derived growth factor C (PDGFC) promotes the progression of lung adenocarcinoma (LUAD) and explores the impact of PDGFC on immune regulation within the tumor microenvironment (TME). Our results show that there is higher expression of PDGFC in CAFs than in nontumor tissue fibroblasts (NFs) and that higher expression of PDGFC is correlated with poor prognosis in LUAD patients. Furthermore, CAF-derived PDGFC promotes epithelial-mesenchymal transition (EMT) in cancer cells as well as matrix metalloproteinase 2 (MMP2) expression through the PDGF receptor A (PDGFRA)-mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway. Moreover, our study demonstrates that CAF-derived PDGFC is essential for the activation and infiltration of fibroblasts in the TME, as well as the inflammatory infiltration of different immune cell types and the immunosuppressive conditions within the TME. In particular, PDGFC induces increased PDGFRA expression in both tumor cells and fibroblasts, which can lead to reciprocally positive feedback to accelerate malignant tumor progression. This discovery provides a novel TME-targeted strategy for LUAD treatment.

Background To elucidate the relationship between cancer-associated fibroblast (CAFs) biomarkers and the prognosis of breast cancer patients for individualized CAFs-targeting treatment. Methodology PubMed, Web of Science, Cochrane, and Embase databases were searched for CAFs-related studies of breast cancer patients from their inception to September, 2023. Meta-analysis was performed using R 4.2.2 software. Sensitivity analyses were performed to explore the sources of heterogeneity. Funnel plot and Egger’s test were used to assess the publication bias. Results Twenty-seven studies including 6,830 patients were selected. Univariate analysis showed that high expression of platelet-derived growth factor receptor-β (PDGFR-β) (P = 0.0055), tissue inhibitor of metalloproteinase-2 (TIMP-2) (P < 0.0001), matrix metalloproteinase (MMP) 9 (P < 0.0001), MMP 11 (P < 0.0001) and MMP 13 (P = 0.0009) in CAFs were correlated with reduced recurrence-free survival (RFS)/disease-free survival (DFS)/metastasis-free survival (MFS)/event-free survival (EFS) respectively. Multivariate analysis showed that high expression of α-smooth muscle actin (α-SMA) (P = 0.0002), podoplanin (PDPN) (P = 0.0008), and PDGFR-β (P = 0.0470) in CAFs was associated with reduced RFS/DFS/MFS/EFS respectively. Furthermore, PDPN and PDGFR-β expression in CAFs of poorly differentiated breast cancer patients were higher than that of patients with relatively better differentiated breast cancer. In addition, there is a positive correlation between the expression of PDPN and human epidermal growth factor receptor-2 (HER-2). Conclusions The high expression of α-SMA, PDPN, PDGFR-β in CAFs leads to worse clinical outcomes in breast cancer, indicating their roles as prognostic biomarkers and potential therapeutic targets.

S100A8/A9 proteins are members of EF-hand calcium-binding proteins secreted by neutrophils and activated monocytes. S100A8/A9 has cell growth-promoting activity at low concentrations by binding to the receptor for advanced glycation end products (RAGE). In this study, we report for the first time that S100A8/A9 promoted the invasion of breast cancer cells depending on RAGE. In addition, RAGE binding to S100A8/A9 promoted the phosphorylation of LIN-11, Isl1, and MEC-3 protein domain kinase, as well as cofilin. This phosphorylation is a critical step in cofilin recycling and actin polymerization. Interestingly, RAGE binding to S100A8/A9 enhanced cell mesenchymal properties and induced epithelial–mesenchymal transition. Mechanistically, RAGE binding to S100A8/A9 stabilized Snail through the NF-κB signaling pathway. Based on these observations, RAGE expression in breast cancer cells was associated with lymph node and distant metastases in patients with invasive ductal carcinoma. Moreover, RAGE binding to S100A8/A9 promoted lung metastasis in vivo. In summary, our in vitro and in vivo results indicated that RAGE binding to S100A8/A9 played an important role in breast cancer invasion/metastasis. This study identified both RAGE and S100A8/A9 as potential anti-invasion targets for therapeutic intervention in breast cancer.

Within the intricate milieu of colorectal cancer (CRC) tissues, cancer-associated fibroblasts (CAFs) act as pivotal orchestrators, wielding considerable influence over tumor progression. This review endeavors to dissect the multifaceted functions of CAFs within the realm of CRC, thereby highlighting their indispensability in fostering CRC malignant microenvironment and indicating the development of CAFs-targeted therapeutic interventions. Through a comprehensive synthesis of current knowledge, this review delineates insights into CAFs-mediated modulation of cancer cell proliferation, invasiveness, immune evasion, and neovascularization, elucidating the intricate web of interactions that sustain the pro-tumor metabolism and secretion of multiple factors. Additionally, recognizing the high level of heterogeneity within CAFs is crucial, as they encompass a range of subtypes, including myofibroblastic CAFs, inflammatory CAFs, antigen-presenting CAFs, and vessel-associated CAFs. Innovatively, the symbiotic relationship between CAFs and the intestinal microbiota is explored, shedding light on a novel dimension of CRC pathogenesis. Despite remarkable progress, the orchestrated dynamic functions of CAFs remain incompletely deciphered, underscoring the need for continued research endeavors for therapeutic advancements in CRC management.

Purpose: Breast cancer poses a huge threat to the lives and health of women worldwide. However, drug resistance makes the treatment of breast cancer challenging. This study aims to investigate the effect of miR-141-3p on paclitaxel resistance and its underlying mechanisms in breast cancer. Methods: Using bioinformatics analysis and qRT-PCR to explore the potential molecule miR-141-3p. Specific binding of miR-141-3p to Keap1 was determined by using a dual luciferase reporter assay. qRT-PCR and Western blot were utilized to observe the expression of miR-141-3p, Keap1, Nrf2, SLC7A11 and GPX4. GSH/GSSG content, MDA content and JC-1 assays were used to observe the ferroptosis levels of breast cancer cells. CCK-8 assay was used to observe the cell viability of breast cancer cells. Tumor subcutaneous transplantation experiment was used to understand the effect of miR-141-3p on paclitaxel resistance in breast cancer in vivo. Results: In the present study, miR-141-3p was found to be highly expressed and associated with poor prognosis in breast cancer. miR-141-3p inhibited Keap1 expression, promoted Nrf2 expression, and facilitated paclitaxel resistance in breast cancer cells. Inhibition of miR-141-3p promoted Keap1 expression, inhibited Nrf2 and its downstream SLC7A11-GSH-GPX4 signaling pathway, as well as promoted ferroptosis in cancer cells, and inhibited paclitaxel and RSL3 resistance. ML385 blocks the effect of miR-141-3p on paclitaxel resistance and ferroptosis resistance in breast cancer cells. In vivo, miR-141-3p mimics promoted paclitaxel resistance, whereas miR-141-3p inhibitors inhibited paclitaxel resistance in breast cancer cells. Conclusion: This work revealed that modulation of the Keap1-Nrf2 signaling pathway by miR-141-3p promoted paclitaxel resistance via regulating ferroptosis in breast cancer cells.

Stroke is a severe neurological disease that is associated with high rates of morbidity and mortality, and the underlying pathological processes are complex. Ferroptosis fulfills a significant role in the progression and treatment of stroke. It is well established that ferroptosis is a type of programmed cell death that is distinct from other forms or types of cell death. The process of ferroptosis involves multiple signaling pathways and regulatory mechanisms that interact with mechanisms inherent to stroke development. Inducers and inhibitors of ferroptosis have been shown to exert a role in the onset of this cell death process. Furthermore, it has been shown that interfering with ferroptosis affects the occurrence of stroke, indicating that targeting ferroptosis may offer a promising therapeutic approach for treating patients of stroke. Hence, the present review aimed to summarize the latest progress that has been made in terms of using therapeutic interventions for ferroptosis as treatment targets in cases of stroke. It provides an overview of the relevant pathways and molecular mechanisms that have been investigated in recent years, highlighting the roles of inducers and inhibitors of ferroptosis in stroke. Additionally, the intervention potential of various types of Traditional Chinese Medicine is also summarized. In conclusion, the present review provides a comprehensive overview of the potential therapeutic targets afforded by ferroptosis‑associated pathways in stroke, offering new insights into how ferroptosis may be exploited in the treatment of stroke.

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived exosomes that transport functional miR-92a from CAFs to tumor cells, thereby intensifying the aggressiveness of breast cancer. CAFs downregulate the expression of G3BP2 in breast cancer cells, and a significant elevation in miR-92a levels in CAF-derived exosomes was observed. Both in vitro and in vivo experiments demonstrate that miR-92a enhances breast cancer cell migration and invasion by directly targeting G3BP2, functioning as a tumor-promoting miRNA. We validated that the RNA-binding proteins SNRPA facilitate the transfer of CAF-derived exosomal miR-92a to breast cancer cells. The reduction of G3BP2 protein by CAF-derived exosomes releases TWIST1 into the nucleus, promoting epithelial-mesenchymal transition (EMT) and further exacerbating breast cancer progression. Moreover, CAF-derived exosomal miR-92a induces tumor invasion and metastasis in mice. Overall, our study reveals that CAF-derived exosomal miR-92a serves as a promoter in the migration and invasion of breast cancer cells by reducing G3BP2 and may represent a potential novel tumor marker for breast cancer.

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL‑1β and IL‑18, as well as gasdermin‑D‑mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3‑mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.

Extrachromosomal circular DNAs (eccDNAs) are defined as distinct genomic entities of circular and mobile DNA molecules, but their molecular functions in and impact on breast cancer (BC) are rarely known. This study used Circle-seq to analyze eccDNAs from 19 BC tissues and 17 adjacent normal tissues. We found that eccDNAs are present on all chromosomes and enriched in seven eccDNA hotspot genes (HSGs) associated with the BC pathway. Several eccDNAs harboring entire genes (eccGenes) and eccDNAs harboring miRNAs (eccMIRs) were identified and linked to cancer-relevant pathways. Synthetic eccMIR6748, eccMIR6508, and eccMIR3142 elevated miRNA expression in MCF-7 cells, with eccMIR6748 promoting BC cell migration and invasion by upregulating miR-6748, which suppresses tumor suppressor candidate factor 5 (TUSC5) at the post-transcriptional level. eccMIR6748 also influences BC progression via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. These findings suggest that eccDNAs, which contain functional genomic segments, play a role in BC initiation and progression, offering a dynamic source of genomic plasticity and potential as biomarkers and therapeutic targets.

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a “first-in-class” drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis.

目的 探讨特异性抑制成纤维细胞活化蛋白(fibro-blast activation protein,FAP)是否能够通过影响肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)的外泌体(exo-somes,exo)抑制内皮细胞间质转化(endothelial-to-mesenchy-mal transition,EndMT)并探究其机制.方法 提取原代CAFs 和癌旁成纤维细胞(peri-tumor fibroblasts,PTFs),收集CAFs-exo 和 PTFs-exo,特异性 FAP 抑制剂(3.3 nmol·L-1 SP13786)处理CAFs 24 h后收集的外泌体命名为Anti-FAP-exo.将内皮细胞HMEC-1分别以等体积的RPMI 1640、PTFs-exo、CAFs-exo 及 Anti-FAP-exo 孵育并命名 为 control组、PTF组、CAF组及Anti-FAP组.划痕实验、Transwell侵袭实验、血管生成实验检测各组HMEC-1细胞的迁移、侵袭及血管生成能力;免疫荧光、免疫组化和Western blot检测EndMT相关蛋白表达水平.结果 CAF组HMEC-1细胞的迁移、侵袭及血管生成能力较PTF组明显增强,Anti-FAP组HMEC-1细胞迁移、侵袭及血管生成能力较CAF组明显减弱,与PTF组比较无差异.与PTF组相比,CAF组HMEC-1细胞高表达α-SMA、SM22α、p-Stat3和Snail,低表达CD31和VE-cadherin;与 CAF 组相比,Anti-FAP 组 HMEC-1 低表达 α-SMA、SM22α、p-Stat3 和 Snail,高表达 CD31 和 VE-cadherin.结论 特异性抑制FAP会通过影响CAFs外泌体间接抑制血管内皮细胞的迁移侵袭与成管能力,Stat3-Snail-EndMT可能是其潜在机制.