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Biomedicine & Pharmacotherapy =... Sep 2022Tumor cells can secret various cytokines and chemokines, which affect the tumor cells themselves and the neighboring cells. Here, we observed that human ovarian cancer...
Tumor cells can secret various cytokines and chemokines, which affect the tumor cells themselves and the neighboring cells. Here, we observed that human ovarian cancer (OC) cells developed resistance to paclitaxel treatment following culture with the conditioned medium (CM) derived from paclitaxel-resistant OC (OC) cells. A cytokine array revealed that both OC cells secreted large amounts of CC chemokine ligand 2 (CCL2). CCL2 and its receptor, CCR2, were overexpressed in OC cells. CCL2 expression was associated with worse progression-free survival in patients with ovarian cancer. The inhibition of the CCL2/CCR2 axis suppressed the chemoresistance induced by OC-CM. The enhanced expression and production of CCL2 in OC cells were mediated via the NF-κB pathway, and stimulated the activation of the PI3K/Akt pathway, which resulted in the development of paclitaxel resistance in OC cells. Additionally, the OC cells significantly increased the migration of macrophages, which was also associated with the overproduction of CCL2 in chemoresistant cancer cells. The macrophages stimulated by OC cells expressed high levels of markers of M2 phenotype, and their CM significantly decreased the paclitaxel responsiveness of OC cells. The administration of a CCR2 inhibitor to a murine model significantly improved the paclitaxel sensitivity. These data suggested that apart from inducing chemoresistance in OC cells by acting as an autocrine factor, CCL2 also functions as a chemokine that induces the chemotaxis of macrophages, which may contribute to chemoresistance. Therefore, targeting the CCL2/CCR2 signaling axis may improve the therapeutic response of patients with ovarian cancer to paclitaxel.
Topics: Animals; Autocrine Communication; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Chemokine CCL2; Chemokines; Cytokines; Female; Humans; Ligands; Macrophages; Mice; Ovarian Neoplasms; Paclitaxel; Phosphatidylinositol 3-Kinases
PubMed: 36076499
DOI: 10.1016/j.biopha.2022.113474 -
Current Opinion in Neurobiology Dec 2022While the history of neuroimmunology is long, the explicit study of neuroimmune communication, and particularly the role of catecholamines in neuroimmunity, is still... (Review)
Review
While the history of neuroimmunology is long, the explicit study of neuroimmune communication, and particularly the role of catecholamines in neuroimmunity, is still emerging. Recent studies have shown that catecholamines, norepinephrine, epinephrine, and dopamine, are central to multiple complex mechanisms regulating immune function. These studies show that catecholamines can be released from both the nervous system and directly from immune cells, mediating both autocrine and paracrine signaling. This commentary highlights the importance of catecholaminergic immunomodulation and discusses new considerations needed to study the role of catecholamines in immune homeostasis to best leverage their contribution to disease processes for the development of new therapeutic approaches.
Topics: Norepinephrine; Dopamine; Catecholamines; Epinephrine; Neuroimmunomodulation
PubMed: 36058009
DOI: 10.1016/j.conb.2022.102626 -
Journal of Animal Science and Technology Jul 2022Spermatogenesis and testis development are highly structured physiological processes responsible for post-pubertal fertility in stallions. Spermatogenesis comprises... (Review)
Review
Spermatogenesis and testis development are highly structured physiological processes responsible for post-pubertal fertility in stallions. Spermatogenesis comprises spermatocytogenesis, meiosis, and spermiogenesis. Although germ cell degeneration is a continuous process, its effects are more pronounced during spermatocytogenesis and meiosis. The productivity and efficiency of spermatogenesis are directly linked to pubertal development, degenerated germ cell populations, aging, nutrition, and season of the year in stallions. The multiplex interplay of germ cells with somatic cells, endocrine and paracrine factors, growth factors, and signaling molecules contributes to the regulation of spermatogenesis. A cell-to-cell communication within the testes of these factors is a fundamental requirement of normal spermatogenesis. A noteworthy development has been made recently on discovering the effects of different somatic cells including Leydig, Sertoli, and peritubular myoid cells on manipulation the fate of spermatogonial stem cells. In this review, we discuss the self-renewal, differentiation, and apoptotic roles of somatic cells and the relationship between somatic and germ cells during normal spermatogenesis. We also summarize the roles of different growth factors, their paracrine/endocrine/autocrine pathways, and the different cytokines associated with spermatogenesis. Furthermore, we highlight important matters for further studies on the regulation of spermatogenesis. This review presents an insight into the mechanism of spermatogenesis, and helpful in developing better understanding of the functions of somatic cells, particularly in stallions and would offer new research goals for developing curative techniques to address infertility/subfertility in stallions.
PubMed: 35969700
DOI: 10.5187/jast.2022.e57 -
International Journal of Molecular... Aug 2022Fibroblast growth factors (FGFs) constitute a large family of signaling molecules that act in an autocrine/paracrine, endocrine, or intracrine manner, whereas the... (Review)
Review
Fibroblast growth factors (FGFs) constitute a large family of signaling molecules that act in an autocrine/paracrine, endocrine, or intracrine manner, whereas the cellular communication network factors (CCN) family is composed of six members that manipulate extracellular signaling networks. FGFs and CCNs are structurally and functionally distinct, except for the common characteristics as matricellular proteins. Both play significant roles in the development of a variety of tissues and organs, including the skeletal system. In vertebrates, most of the skeletal parts are formed and grow through a process designated endochondral ossification, in which chondrocytes play the central role. The growth plate cartilage is the place where endochondral ossification occurs, and articular cartilage is left to support the locomotive function of joints. Several FGFs, including FGF-2, one of the founding members of this family, and all of the CCNs represented by CCN2, which is required for proper skeletal development, can be found therein. Research over a decade has revealed direct binding of CCN2 to FGFs and FGF receptors (FGFRs), which occasionally affect the biological outcome via FGF signaling. Moreover, a recent study uncovered an integrated regulation of FGF and CCN genes by FGF signaling. In this review, after a brief introduction of these two families, molecular and genetic interactions between CCN and FGF family members in cartilage, and their biological effects, are summarized. The molecular interplay represents the mutual involvement of the other in their molecular functions, leading to collaboration between CCN2 and FGFs during skeletal development.
Topics: Animals; Cartilage; Chondrocytes; Fibroblast Growth Factors; Growth Plate; Receptors, Fibroblast Growth Factor
PubMed: 35955724
DOI: 10.3390/ijms23158592 -
Frontiers in Genetics 2022Traditionally, cancer-associated fibroblasts (CAFs), an essential component of tumor microenvironment, were exert a crucial part in colon cancer progression. In this...
Traditionally, cancer-associated fibroblasts (CAFs), an essential component of tumor microenvironment, were exert a crucial part in colon cancer progression. In this study, single-cell RNA-sequencing (scRNA-seq) data from 23 and bulk RNA-seq data from 452 colon cancer patients were extracted from the GEO database and TCGA-COAD and GEO databases, respectively. From single-cell analysis, 825 differentially expressed genes (DEGs) in CAFs were identified between each pair of six newly defined CAFs, named enCAF, adCAF, vaCAF, meCAF, erCAF, and cyCAF. Cell communication analysis with the iTALK package showed communication relationship between CAFs, including cell autocrine, cytokine, and growth factor subtypes, such as receptor-ligand pairs of , and . Herein, we demonstrated the presence and prognostic value of adCAF and erCAF in colon cancer based on CIBERSORTx, combining single-cell marker genes and transcriptomics data. The prognostic significance of the enCAF and erCAF has been indirectly proved by both the correlation analysis with macrophages and CAFs, and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) experiment based on 20 paired tumor samples. A prognostic model was constructed with 10 DEGs using the LASSO Cox regression method. The model was validated using two testing datasets, indicate a significant survival accuracy ( < 0.0025). Correlation analyses between clinical information, such as age, gender, tumor stage and tumor features (tumor purity and immune score), and risk scores revealed our CAF-related model's robustness and excellent performance. Cell infiltration analysis by xCell revealed that the interaction between CAFs and multiple non-specific immune cells such as macrophages and the dendritic cell was a vital factor affecting immune score and prognosis. Finally, we analyzed how common anti-cancer drugs, including camptothecin, docetaxel and bortezomib, and immunotherapy, such as anti-PD-1 treatment, could be different in low-risk and high-risk patients inferred from our CAF-related model. In conclusion, the study utilized refined colon cancer fibroblast subsets and established the prognostic effects from the interaction with nonspecific immune cell.
PubMed: 35910200
DOI: 10.3389/fgene.2022.908957 -
Nature Communications Jul 2022Fate determination and maintenance of fetal testes in most mammals occur cell autonomously as a result of the action of key transcription factors in Sertoli cells....
Fate determination and maintenance of fetal testes in most mammals occur cell autonomously as a result of the action of key transcription factors in Sertoli cells. However, the cases of freemartin, where an XX twin develops testis structures under the influence of an XY twin, imply that hormonal factor(s) from the XY embryo contribute to sex reversal of the XX twin. Here we show that in mouse XY embryos, Sertoli cell-derived anti-Mullerian hormone (AMH) and activin B together maintain Sertoli cell identity. Sertoli cells in the gonadal poles of XY embryos lacking both AMH and activin B transdifferentiate into their female counterpart granulosa cells, leading to ovotestis formation. The ovotestes remain to adulthood and produce both sperm and oocytes, although there are few of the former and the latter fail to mature. Finally, the ability of XY mice to masculinize ovaries is lost in the absence of these two factors. These results provide insight into fate maintenance of fetal testes through the action of putative freemartin factors.
Topics: Activins; Animals; Anti-Mullerian Hormone; Autocrine Communication; Cell Differentiation; Female; Male; Mammals; Mice; Paracrine Communication; Semen; Sertoli Cells; Testis
PubMed: 35840551
DOI: 10.1038/s41467-022-31486-y -
Frontiers in Physiology 2022The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male infertility has lately received significant attention. SARS-CoV-2, the virus that... (Review)
Review
The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on male infertility has lately received significant attention. SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) in humans, has been shown to impose adverse effects on both the structural components and function of the testis, which potentially impact spermatogenesis. These adverse effects are partially explained by fever, systemic inflammation, oxidative stress, and an increased immune response leading to impaired blood-testis barrier. It has been well established that efficient cellular communication gap junctions or functional channels is required for tissue homeostasis. Connexins and pannexins are two protein families that mediate autocrine and paracrine signaling between the cells and the extracellular environment. These channel-forming proteins have been shown to play a role in coordinating cellular communication in the testis and epididymis. Despite their role in maintaining a proper male reproductive milieu, their function is disrupted under pathological conditions. The involvement of these channels has been well documented in several physiological and pathological conditions and their designated function in infectious diseases. However, their role in COVID-19 and their meaningful contribution to male infertility remains to be elucidated. Therefore, this review highlights the multivariate pathophysiological mechanisms of SARS-CoV-2 involvement in male reproduction. It also aims to shed light on the role of connexin and pannexin channels in disease progression, emphasizing their unexplored role and regulation of SARS-CoV-2 pathophysiology. Finally, we hypothesize the possible involvement of connexins and pannexins in SARS-CoV-2 inducing male infertility to assist future research ideas targeting therapeutic approaches.
PubMed: 35721552
DOI: 10.3389/fphys.2022.866675 -
Frontiers in Molecular Biosciences 2022In the past decade, the focus of bottom-up synthetic biology has shifted from the design of complex artificial cell architectures to the design of interactions between... (Review)
Review
In the past decade, the focus of bottom-up synthetic biology has shifted from the design of complex artificial cell architectures to the design of interactions between artificial cells mediated by physical and chemical cues. Engineering communication between artificial cells is crucial for the realization of coordinated dynamic behaviours in artificial cell populations, which would have implications for biotechnology, advanced colloidal materials and regenerative medicine. In this review, we focus our discussion on molecular communication between artificial cells. We cover basic concepts such as the importance of compartmentalization, the metabolic machinery driving signaling across cell boundaries and the different modes of communication used. The various studies in artificial cell signaling have been classified based on the distance between sender and receiver cells, just like in biology into autocrine, juxtacrine, paracrine and endocrine signaling. Emerging tools available for the design of dynamic and adaptive signaling are highlighted and some recent advances of signaling-enabled collective behaviours, such as quorum sensing, travelling pulses and predator-prey behaviour, are also discussed.
PubMed: 35720123
DOI: 10.3389/fmolb.2022.880525 -
Cells May 2022Matrix vesicles are key players in the development of the growth plate during endochondral bone formation. They are involved in the turnover of the extracellular matrix... (Review)
Review
Matrix vesicles are key players in the development of the growth plate during endochondral bone formation. They are involved in the turnover of the extracellular matrix and its mineralization, as well as being a vehicle for chondrocyte communication and regulation. These extracellular organelles are released by the cells and are anchored to the matrix via integrin binding to collagen. The exact function and makeup of the vesicles are dependent on the zone of the growth plate in which they are produced. Early studies defined their role as sites of initial calcium phosphate deposition based on the presence of crystals on the inner leaflet of the membrane and subsequent identification of enzymes, ion transporters, and phospholipid complexes involved in mineral formation. More recent studies have shown that they contain small RNAs, including microRNAs, that are distinct from the parent cell, raising the hypothesis that they are a distinct subset of exosomes. Matrix vesicles are produced under complex regulatory pathways, which include the action of steroid hormones. Once in the matrix, their maturation is mediated by the action of secreted hormones. How they convey information to cells, either through autocrine or paracrine actions, is now being elucidated.
Topics: Calcification, Physiologic; Calcinosis; Extracellular Matrix; Extracellular Vesicles; Hormones; Humans; Osteogenesis
PubMed: 35626656
DOI: 10.3390/cells11101619 -
Nature Jun 2022T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. In comparison with other organs,...
T cell development in the thymus is essential for cellular immunity and depends on the organotypic thymic epithelial microenvironment. In comparison with other organs, the size and cellular composition of the thymus are unusually dynamic, as exemplified by rapid growth and high T cell output during early stages of development, followed by a gradual loss of functional thymic epithelial cells and diminished naive T cell production with age. Single-cell RNA sequencing (scRNA-seq) has uncovered an unexpected heterogeneity of cell types in the thymic epithelium of young and aged adult mice; however, the identities and developmental dynamics of putative pre- and postnatal epithelial progenitors have remained unresolved. Here we combine scRNA-seq and a new CRISPR-Cas9-based cellular barcoding system in mice to determine qualitative and quantitative changes in the thymic epithelium over time. This dual approach enabled us to identify two principal progenitor populations: an early bipotent progenitor type biased towards cortical epithelium and a postnatal bipotent progenitor population biased towards medullary epithelium. We further demonstrate that continuous autocrine provision of Fgf7 leads to sustained expansion of thymic microenvironments without exhausting the epithelial progenitor pools, suggesting a strategy to modulate the extent of thymopoietic activity.
Topics: Aging; Animals; Autocrine Communication; CRISPR-Cas Systems; Cellular Microenvironment; Epithelial Cells; Epithelium; Fibroblast Growth Factor 7; Mice; RNA-Seq; Single-Cell Analysis; Stem Cells; T-Lymphocytes; Thymus Gland
PubMed: 35614226
DOI: 10.1038/s41586-022-04752-8