Melanoma Stem Cells, Vasculogenesis and Neoplastic Progression

摘要： 人黑色素瘤是一种高度侵袭性和耐药性的癌症，一旦全身治疗就有抗药性。 传播。在这种恶性肿瘤中发现具有胚胎样可塑性的未分化亚群 指出了黑色素瘤干细胞的存在最近我们的实验室已经确定了黑色素瘤干细胞 以表达化学抗性介质ABCBS为特征的细胞，ABCBS负责 黑色素瘤进展，并且可以在实验性肿瘤异种移植模型中进行治疗靶向。 黑色素瘤干细胞触发肿瘤发生和促进肿瘤生长的分子和细胞机制 肿瘤进展目前尚不清楚。血管生成和转移是公认的现象， 对肿瘤生长和肿瘤进展至关重要。尽管我们对分子生物学 虽然癌症干细胞与这些过程之间的特定关系尚未得到证实， 迄今我们假设黑色素瘤干细胞具有自我更新和分化的能力， 负责肿瘤生长，可能与肿瘤生长中关键参与的癌症亚群一致。 血管发生和转移以及该细胞群和相关分子特异性靶向 因此，通路可以提供新的策略，以根除目前对常规化疗耐药的癌症。 疗法本研究的具体目标是：（1）研究ABCBS+与 黑色素瘤干细胞和肿瘤血管发生，并定义所涉及的分子机制;（2）定义 ABCBS+黑色素瘤干细胞在转移性肿瘤进展中的作用;和（3）开发新的黑色素瘤 干细胞靶向治疗因此，该提议与旨在开发新颖的 基于选择性靶向癌干细胞中重要分子通路的癌症治疗策略 细胞

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.