Melanoma Stem Cells, Vasculogenesis and Neoplastic Progression

黑色素瘤干细胞、血管生成和肿瘤进展

• 批准号: 8307737
• 负责人: Markus H. Frank
• 金额: $ 33.66万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-24 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307737
• 关键词: Adult; Binding; Breslow Thickness; Cell Line; Cells; Clinical; Diagnosis; Disease Progression; Disseminated Malignant Neoplasm; Drug resistance; Early Diagnosis; Embryo; Excision; Experimental Neoplasms; Failure; Family; Gene Expression; Genes; Growth; Human; Humpback Dolphins; In Vitro; Infiltration; Knowledge; Laboratories; Malignant Neoplasms; Mediator of activation protein; Melanoma Cell; Minority; Modeling; Molecular; Molecular Profiling; Multi-Drug Resistance; Neoplasm Metastasis; Operative Surgical Procedures; Pathway interactions; Patients; Pattern; Population; Process; Radial Growth Phase; Resistance; Role; Stem cells; Survival Rate; Systemic Therapy; Therapeutic; Treatment Protocols; Tumor Stem Cells; Undifferentiated; Visceral; Work; Xenograft procedure; abstracting; base; cancer stem cell; cancer therapy; chemotherapy; conventional therapy; improved; lifetime risk; lymph nodes; melanoma; member; mimicry; mortality; novel; novel strategies; novel therapeutics; outcome forecast; self-renewal; therapy resistant; tumor; tumor growth; tumor initiation; tumor progression; tumorigenesis; vasculogenesis

Abstract: Human melanoma is a highly aggressive and drug resistant cancer and resistant to systemic therapy once disseminated. Findings of undifferentiated subpopulations with embryonic-like plasticity within this malignancy have pointed to the presence of melanoma stem cells. Recently our laboratory has identified melanoma stem cells characterized by expression of the chemoresistance mediator ABCBS, which are responsible for melanoma progression and can be therapeutically targeted in experimental tumor xenotransplantation models. The molecular and cellular mechanisms by which melanoma stem cells trigger tumorigenesis and promote neoplastic progression are currently unknown. Vasculogenesis and metastasis are phenomena recognized to be critical for tumor growth and neoplastic progression. Despite the significant knowledge about the molecular pathways involved, a specific relationship of cancer stem cells to these processes has not been demonstrated to date. We hypothesize that melanoma stem cells capable of self-renewal and differentiation, which are responsible for tumor growth, may coincide with cancer subpopulations critically involved in tumor vasculogenesis and metastasis and that specific targeting of this cell population and of related molecular pathways could thus provide for novel strategies to eradicate cancers currently resistant to conventional therapy. The specific aims of this proposal are the following: (1) Investigate the relationship between ABCBS+ melanoma stem cells and tumor vasculogenesis and define the molecular mechanisms involved; (2) Define the role of ABCBS+ melanoma stem cells in metastatic neoplastic progression; and (3) Develop novel melanoma stem cell-targeted therapies. Thus, the proposal is highly relevant to efforts directed at developing novel therapeutic strategies to cancer therapy based on selectively targeting vital molecular pathways in cancer stem cells.

文摘:

项目成果

Effects of Malignant Melanoma Initiating Cells on T-Cell Activation.

恶性黑色素瘤起始细胞对 T 细胞激活的影响。

• DOI: 10.1007/7651_2015_299
• 发表时间: 2016
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Schatton,Tobias;Schütte,Ute;Frank,MarkusH
• 通讯作者: Frank,MarkusH