Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death,motility, migration, and stemness. These systems are not only commonly activated in many so...Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death,motility, migration, and stemness. These systems are not only commonly activated in many solid tumors, where they drive or contribute to cancer initiation, but also in primary and metastatic tumor development. The reactivation of developmental pathways in cancer stroma favors the development of cancer stem cells and allows their maintenance, indicating these signaling pathways as particularly attractive targets for efficient anticancer therapies, especially in advanced primary tumors and metastatic cancers. Metastasis is the worst feature of cancer development. This feature results from a cascade of events emerging from the hijacking of epithelial-mesenchymal transition, angiogenesis, migration, and invasion by transforming cells and is associated with poor survival, drug resistance, and tumor relapse. In the present review, we summarize and discuss experimental data suggesting pivotal roles for developmental pathways in cancer development and metastasis, considering the therapeutic potential. Emerging targeted antimetastatic therapies based on Notch, Wnt, and Hedgehog pathways are also discussed.展开更多
Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. Thes...Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like "wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.展开更多
After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discr...After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discrepancies.We discuss the pro-tumorigenic effects of stromal cells,considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells,as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment,and cancer initiating cells'cellular senescence and adaptive metabolism.We summarize the emerging data supporting stromal cell therapeutic potential in cancer,discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects,and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.展开更多
Microbial-induced inflammation serves a dual role,safeguarding against pathogens but also posing a risk of secondary harm to host tissues,potentially leading to fibrosis and cancer.Beyond traditional pathogens,gut mic...Microbial-induced inflammation serves a dual role,safeguarding against pathogens but also posing a risk of secondary harm to host tissues,potentially leading to fibrosis and cancer.Beyond traditional pathogens,gut microbiota,the mutualistic microorganisms inhabiting the gastrointestinal tract,crucial for digestion,immunity,and cancer prevention,can incite inflammation-related cancer when their microenvironment undergoes changes.Recent research reveals that microbiota members like Escherichia coli and other genotoxic pathogens can induce DNA damage across various cell types.Chronic infections involving microbiota members like Helicobacter spp.,linked to liver,colorectal,cervical cancers,and lymphoma,can activate carcinogenic processes.Inflammatory responses,driven by immune cells releasing inflammatory molecules like macrophage migration inhibitory factor(MMIF),superoxide peroxynitrite,pro-inflammatory cytokines,adhesion molecules,and growth factors,contribute to DNA damage and oncogenic mutations accumulation.This microenvironment further supports neoplastic cell survival and proliferation.This summary discusses the involvement of inflammatory pathways in microbial-triggered carcinogenesis and the potential role of microbiota modulation in cancer prevention.展开更多
文摘Master developmental pathways, such as Notch, Wnt, and Hedgehog, are signaling systems that control proliferation, cell death,motility, migration, and stemness. These systems are not only commonly activated in many solid tumors, where they drive or contribute to cancer initiation, but also in primary and metastatic tumor development. The reactivation of developmental pathways in cancer stroma favors the development of cancer stem cells and allows their maintenance, indicating these signaling pathways as particularly attractive targets for efficient anticancer therapies, especially in advanced primary tumors and metastatic cancers. Metastasis is the worst feature of cancer development. This feature results from a cascade of events emerging from the hijacking of epithelial-mesenchymal transition, angiogenesis, migration, and invasion by transforming cells and is associated with poor survival, drug resistance, and tumor relapse. In the present review, we summarize and discuss experimental data suggesting pivotal roles for developmental pathways in cancer development and metastasis, considering the therapeutic potential. Emerging targeted antimetastatic therapies based on Notch, Wnt, and Hedgehog pathways are also discussed.
文摘Mesenchymal stromal cells(MSCs) are adult multipotent stem cells residing as pericytes in various tissues and organs where they can differentiate into specialized cells to replace dying cells and damaged tissues. These cells are commonly found at injury sites and in tumors that are known to behave like "wounds that do not heal." In this article, we discuss the mechanisms of MSCs in migrating, homing, and repairing injured tissues. We also review a number of reports showing that tumor microenvironment triggers plasticity mechanisms in MSCs to induce malignant neoplastic tissue formation, maintenance, and chemoresistance, as well as tumor growth. The antitumor properties and therapeutic potential of MSCs are also discussed.
文摘After more than a decade of controversy on the role of stromal cells in the tumor microenvironment,the emerging data shed light on pro-tumorigenic and potential anti-cancer factors,as well as on the roots of the discrepancies.We discuss the pro-tumorigenic effects of stromal cells,considering the effects of tumor drivers like hypoxia and tumor stiffness on these cells,as well as stromal cell-mediated adiposity and immunosuppression in the tumor microenvironment,and cancer initiating cells'cellular senescence and adaptive metabolism.We summarize the emerging data supporting stromal cell therapeutic potential in cancer,discuss the possibility to reprogram stromal cells of the tumor microenvironment for anti-cancer effects,and explore some causes of discrepancies on the roles of stromal cells in cancer in the available literature.
文摘Microbial-induced inflammation serves a dual role,safeguarding against pathogens but also posing a risk of secondary harm to host tissues,potentially leading to fibrosis and cancer.Beyond traditional pathogens,gut microbiota,the mutualistic microorganisms inhabiting the gastrointestinal tract,crucial for digestion,immunity,and cancer prevention,can incite inflammation-related cancer when their microenvironment undergoes changes.Recent research reveals that microbiota members like Escherichia coli and other genotoxic pathogens can induce DNA damage across various cell types.Chronic infections involving microbiota members like Helicobacter spp.,linked to liver,colorectal,cervical cancers,and lymphoma,can activate carcinogenic processes.Inflammatory responses,driven by immune cells releasing inflammatory molecules like macrophage migration inhibitory factor(MMIF),superoxide peroxynitrite,pro-inflammatory cytokines,adhesion molecules,and growth factors,contribute to DNA damage and oncogenic mutations accumulation.This microenvironment further supports neoplastic cell survival and proliferation.This summary discusses the involvement of inflammatory pathways in microbial-triggered carcinogenesis and the potential role of microbiota modulation in cancer prevention.
