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Developmental pathways associated with cancer metastasis:Notch,Wnt,and Hedgehog

Cancer Biology & Medicine 2017年第2期14卷 109-120页

作者： Armel Herve Nwabo Kamdje Paul Takam Kamga Richard Tagne Simo Lorella Vecchio Paul Faustin Seke Etet Jean Marc Muller Giulio Bassi erique lukong Raghuveera Kumar Goel Jeremie Mbo Amvene Mauro Krampera Department of Biomedical Sciences University of Ngaoundere Laboratory University of Verona Department of Basic Health SciencesCollege of Applied Medical SciencesQassim University Faculty of Science University of Poitiers Department of Biochemistry College of MedicineUniversity of Saskatchewan

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.

关键词： Hedgehog 肿瘤干细胞 Notch Wnt 移相信号系统细胞增殖信号通路

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Mesenchymal stromal cells' role in tumor microenvironment:involvement of signaling pathways

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Cancer Biology & Medicine 2017年第2期14卷 129-141页

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.

关键词：基质细胞肿瘤组织微环境信号通路骨髓间充质干细胞间质组织损伤 MSCs

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Emerging data supporting stromal cell therapeutic potential in cancer:reprogramming stromal cells of the tumor microenvironment for anti-cancer effects

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Cancer Biology & Medicine 2020年第4期17卷 828-841页

作者： Armel H.Nwabo Kamdje Paul F.Seke Etet Richard Tagne Simo Lorella Vecchio Kiven erique lukong Mauro Krampera Department of Biomedical Sciences University of NgaoundereFaculty of ScienceNgaoundere 454Cameroon Department of Physiological Sciences and Biochemistry University of NgaoundereGaroua 454Cameroon Center for Sustai nable Health and Development Garoua 454Cameroon Department of Biochemistry Microbiology&ImmunologyUniversity of SaskatchewanCollege of MedicineSaskatoon SK S7N 5E5Canada Department of Medicine University of VeronaSection of HematologyStem Cell Research LaboratoryVerona 37134Italy

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.

关键词： Stromal cells tumorigenic effects anti-cancer effects tumor microenvironment reprogramming

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New targeted therapies for breast cancer: A focus on tumor microenvironmental signals and chemoresistant breast cancers

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World Journal of Clinical Cases 2014年第12期2卷 769-786页

作者： Armel Hervé Nwabo Kamdje Paul Faustin Seke Etet Lorella Vecchio Richard Simo Tagne Jeremie Mbo Amvene Jean-Marc Muller Mauro Krampera Kiven erique lukong Department of Biomedical Sciences Faculty of Sciences University of NgaoundéréPO Box 454 NgaoundéréCameroon Department of Basic Health Sciences College of Applied Medical Sciences Qassim UniversityBuraydah 52571 Saudi Arabia Université de Poitiers Faculté des Sciences P?le Biologie-Santé Bat B36 1 rue Georges Bonnet-BP633 86022 Poitiers cedex France Department of Medicine Section of Hematology Stem Cell Research Laboratory University of Verona 37129 Verona Italy Department of Biochemistry College of Medicine University of Saskatchewan Saskatoon S7N 5E5 Canada

Breast cancer is the most frequent female malignancy worldwide. Current strategies in breast cancer therapy,including classical chemotherapy, hormone therapy, and targeted therapies, are usually associated with chemoresistance and serious adverse effects. Advances in our understanding of changes affecting the interactome in advanced and chemoresistant breast tumors have provided novel therapeutic targets, including, cyclin dependent kinases, mammalian target of rapamycin,Notch, Wnt and Shh. Inhibitors of these molecules recently entered clinical trials in mono- and combination therapy in metastatic and chemo-resistant breast cancers. Anticancer epigenetic drugs, mainly histone deacetylase inhibitors and DNA methyltransferase inhibitors, also entered clinical trials. Because of the complexity and heterogeneity of breast cancer, the future in therapy lies in the application of individualized tailored regimens. Emerging therapeutic targets and the implications for personalized-based therapy development in breast cancer are herein discussed.

关键词： Breast cancer Microenvironment Signaling molecule Targeted therapy Chemoresistance

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