Cell Biology International最新文献

The Signaling Lymphocytic Activation Molecule (SLAM) family receptors play essential roles in regulating immune cell activation, differentiation, and communication. SLAMF5, also known as CD84, has drawn increasing attention in cancer immunology due to its involvement in both tumor progression and immune modulation. This review explores the expression patterns, signaling mechanisms, and functional roles of SLAMF5/CD84 within the tumor microenvironment. SLAMF5/CD84 is expressed on multiple immune cell types and contributes to immune evasion by enhancing regulatory B cell function, promoting myeloid-derived suppressor cell expansion, and upregulating immune checkpoint molecules such as PD-L1. Its expression has been implicated in various hematologic malignancies and solid tumors, including chronic lymphocytic leukemia, multiple myeloma, and triple-negative breast cancer. Emerging therapeutic approaches targeting SLAMF5/CD84—such as monoclonal antibodies and CAR T-cell therapies—offer promising strategies to counteract immunosuppression and improve treatment outcomes. By highlighting recent findings and therapeutic developments, this review underscores the significance of SLAMF5/CD84 as both a prognostic biomarker and a novel target in cancer immunotherapy. Understanding SLAMF5/CD84's multifaceted roles in the tumor immune landscape could support the development of more effective and personalized cancer treatment strategies.

Breast cancer (BC) is a frequently diagnosed neoplasm in women and the second major cause of cancer-related deaths. Many BC patients develop metastasis and advanced tumors, increasing morbidity and mortality. There is substantial evidence that tumor relapses in BC patients are driven by a unique population of cells called cancer stem cells (CSCs). Breast CSCs confer stemness to BC and survive through the maintenance of several mechanisms, among which is the involvement of the mTOR signaling pathway. mTOR and its associated AKT signaling play a crucial role in regulating CSCsin various human cancers, including breast cancer. This study investigated the role of targeting mTOR/AKT signaling in the modulation of cell death in 2D and 3D breast cancer models. Torin-2, a dual mTOR inhibitor, effectively suppressed cell proliferation by inducing mitochondrial apoptosis. The inhibition of mTOR led to a decrease in AKT activity and downregulation of key translational machinery components, including 4EBP1, eIF4E, and p70S6K. Torin-2 treatment activated autophagy signaling in both 2D and 3D cell models. The induction of autophagy was evidenced by an increase in the autophagy protein LC3II/I in response to Torin-2 treatment. In addition, Torin-2 treatment of spheroids derived from breast cancer cells suppressed the expression of stem cell marker ALDH. Altogether, the dual inhibition of mTORC1 and mTORC2 by Torin-2 resulted in a more profound antitumor activity. This broader and more potent inhibition of the mTOR pathway contributes to effectiveness in suppressing 2D and 3D breast cancer cell growth and survival.

The second most significant contributor to the global mortality rate resulting from non-communicable diseases is cancer. Cancer cells are recognized for their interactions with adjacent noncancerous cells, such as immune and stromal cells, within the tumor microenvironment, which play a crucial role in influencing tumor progression, metastasis, and resistance. T cell activation is a pivotal process that facilitates the immune system's ability to combat malignancies, characterized by a multi-step signaling cascade leading to T cell proliferation and differentiation. During this activation phase, T cells release a variety of extracellular vesicles, particularly exosomes, which serve as critical regulators of intercellular communication within the tumor microenvironment. These vesicles contain bioactive molecules such as proteins, microRNAs, and immunomodulatory factors that influence tumor growth, immune evasion, and therapeutic responses. CD8⁺T cell-derived exosomes (CD8⁺T-Exos) have been shown to inhibit tumor metastasis by carrying microRNAs that downregulate tumor-promoting genes while also enhancing immune responses by activating CD8⁺T lymphocytes. By elucidating the diverse functions of CD8⁺T-Exos, this review highlights their potential as both biomarkers and therapeutic agents in cancer treatment.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by abnormal bone resorption. Anti-citrullinated protein/peptide antibodies (ACPAs), detected in most RA patients, can stimulate osteoclasts differentiation by targeting osteoclast precursors, thereby enhancing bone resorption. However, the underlying mechanism of ACPAs-induced osteoclast activation on bone resorption in RA remains unknown. In this study, ACPA-positive (ACPA⁺) IgG promoted the maturation of osteoclasts. Phalloidin and wheat germ agglutinin (WGA) staining demonstrated that the ACPA⁺ IgG group exhibited significantly higher mean fluorescence intensity, cell volume, and wheat agglutinin coloring in osteoclasts compared to the ACPA-negative (ACPA⁻) IgG group. Additionally, ACPA⁺ IgG stimulation significantly upregulated the p-SYK/SYK ratio in osteoclasts. SYK knockdown had no effect on osteoblast differentiation, but significantly decreased the area of bone lacunae, and attenuated osteoclasts bone resorption. Furthermore, SYK knockdown significantly decreased Vav3 phosphorylation, and colocalization of SYK and Vav3 was observed in osteoclasts. Notably, SYK and Vav3 enrichment at the leading edge of the osteoclasts was abrogated in the SYK-shRNA group. The number of actin rings was also significantly lower in the SYK-shRNA group compared to the SYK-shRNA-NC group. In conclusion, ACPA⁺ IgG induction not only promoted osteoclastogenesis but also increased SYK phosphorylation and bone resorption. SYK exacerbated osteoclast bone resorption by promoting Vav3 phosphorylation. These findings provide valuable insights for identifying novel therapeutic targets in RA.

Modernizing traditional Chinese medicine (TCM) requires preserving its foundational principles while integrating contemporary innovations and clarifying therapeutic methods. Organoids and organoids-on-chip technologies offer advanced models of human organs, and serve as an excellent platform for investigating TCM theories and complex herbal formulas. To systematically summarize recent progress in using organoids and organoids-on-chip in TCM research, and critically assess their technical advantages and future potential, relevant articles and information were sourced from scientific databases such as PubMed, SpringerLink, Web of Science, ScienceDirect, and VIP. The application of organoids and organoids-on-chip technologies in TCM research encompasses theory interpretation, efficacy evaluation, mechanism elucidation, toxicity assessment, active ingredient screening, and formula optimization. These applications offer significant advantages, such as unveiling holistic effects, deciphering mechanistic bases through dynamic visualization approaches, and demonstrating personalized therapeutic benefits. Enhancing physiological relevance, automation, and intelligent applications are future development directions. Organoids and organoids-on-chip represent transformative tools for the modernization of TCM. Future advancements in vascularization, neural network development, and the integration of artificial intelligence are anticipated to address existing limitations, thereby enhancing physiological relevance and clinical translation. These advancements are expected to promote global acceptance and innovation in TCM.

Colonization of Helicobacter pylori (H. pylori) in stomach often causes gastritis, an inflammation of the stomach lining that is closely associated with serious conditions like ulcers and gastric cancer. Of the toxicity mechanisms, microbial lipopolysaccharide (LPS) binding to TLR4 receptor on the glandular cells activates the NF-κB pathway, inducing pro-inflammatory cytokine release and immune cell infiltration, which results in the tissue damage. However, whether LPS has any direct damaging effect on gastric epithelial cells has been in debate. By using mouse gastric organoids that were grown from the isolated glands and maintained the cellular compositions, we demonstrate various effects of variable LPS concentrations on the glandular epithelial cells, including mild promotion of cell proliferation at the low concentration and induced loss of cell polarity and altered gene expressions at the high concentration. These findings provide insights into how LPS directly affects the stomach lining.

Most evidence obtained to date suggests a pivotal role for lactate in the control of tumor growth and metastasis. However, the precise mechanism by which lactate decreases tumor cell death remains incompletely defined. Here, we report that parthanatos, a kind of poly (ADP-ribose) polymerase-1 (PARP1) dependent but caspase-independent programmed cell death, does occur in two gastric cancer cell lines (MKN28 and MGC803) under glucose-deprived conditions. Lactate prevented the glucose deprivation-induced parthanatos in an acid-independent manner. In addition, glucose deprivation increased intracellular reactive oxygen species (ROS) generation, whereas lactate reduces ROS levels by promoting NADPH generation. AG120, a selective inhibitor of isocitrate dehydrogenase 1 (IDH1) that catalyzes cytosolic NADPH generation, effectively eliminated the effect of lactate on NADPH generation and reversed the protective effect of lactate on glucose deprivation-induced parthanatos. Similar effects were also observed when lactate dehydrogenase B (LDHB) was knocked down. Our findings reveal that lactate prevents glucose deprivation-induced parthanatos in gastric cancer cells by alleviating intracellular oxidative stress, reflecting a new mechanism by which lactate facilitates the adaptation of tumor cells to the nutrient-deficient tumor microenvironment and promotes tumor development.

Fibroblasts are pivotal cellular components in cutaneous wound healing and are regarded as promising therapeutic candidates. However, their functional heterogeneity within tissue microenvironments significantly limits their clinical application. In contrast, whether fibroblast-derived extracellular vesicles (EVs) can overcome fibroblast heterogeneity while retaining the bioactivity and regenerative potential of homeostatic fibroblasts remains unclear. In this study, we systematically analyzed and compared the therapeutic potential and functional advantages of human dermal fibroblast-derived EVs (hDF-EVs) in promoting cutaneous wound healing. Our findings highlight the translational potential of fibroblast-derived EVs as a novel strategy to improve clinical outcomes for skin injuries. hDF-EVs were internalized by fibroblasts and keratinocytes at the wound margins, thereby attenuating early inflammatory responses and accelerating tissue repair following dermal excisional injuries. hDF-EVs significantly enhanced the proliferation and migration of both fibroblasts and keratinocytes in a coculture system. Transcriptomic analysis revealed that hDF-EVs upregulated genes involved in cell proliferation and cytokine regulation. Integrated miRNA profiling revealed a subset of hDF-EVs-enriched miRNAs that mechanistically orchestrate fibroblast activation through coordinated MAPK, Wnt, and Ras signaling axis engagement, consequently reprogramming inflammatory mediator secretion dynamics in wound microenvironments. Furthermore, cytokine array analysis demonstrated that hDF-EVs enhanced the expression of various cytokines, including Amphiregulin, GCSF, IL-7, and IL-2, while activating Ras, Rap1, PI3K-Akt, and MAPK signaling pathways during the early stage of wound healing. Collectively, hDF-EVs promote wound healing by modulating early growth factor dynamics and enhancing fibroblast-keratinocyte crosstalk, presenting a novel cell-free strategy for skin regeneration.

Transcription factor AP-2 gamma (TFAP2C) plays a pro-cancer role in various malignancies. Yet, the action of TFAP2C in glioblastoma (GBM) is unknown. This study aimed to investigate the effects of TFAP2C in GBM and the potential mechanism. TFAP2C knockdown in GBM cell lines was employed to examine its impact on cell proliferation, migration, and invasion (PMI), as well as epithelial-mesenchymal transition (EMT) development, and its association with the PI3K/AKT/mTOR (PAM) pathway by co-overexpressing PI3K or SC79 treatment (AKT agonist). The binding of TFAP2C and the PI3K promoter was predicted and validated. Finally, the above effects and mechanisms were verified in in vivo animal experiments. TFAP2C expression was strikingly heightened in human GBM cell lines and showed a negative correlation with patient survival. TFAP2C silencing inhibited GBM cell PMI, N-cadherin and Vimentin expression, and the PAM pathway, and activated E-cadherin and ZO-1 expression. Overexpression of PI3K or SC79 treatment reversed the above changes, suggesting that TFAP2C promotes GBM cell PMI and EMT via the PAM pathway. Mechanistically, TFAP2C binds to the promoter of PI3K and regulates PI3K transcription. Finally, the in vitro results were further validated in animal experiments. In conclusion, TFAP2C promotes PI3K transcription through direct binding to the promoter of PI3K and activates the PAM pathway to promote GBM proliferation and EMT, providing a potential therapeutic target for GBM.