Gesundheit Benjamin, Malach Lea, Or Reuven, Hahn Talia
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Cancer Microenviron. 2008 Dec;1(1):153-7. doi: 10.1007/s12307-008-0015-2. Epub 2008 Aug 27.
Three phenotypically distinct cell types are present in human neuroblastomas (NB) and NB cell lines: I-type stem cells, N-type neuroblastic precursors, and S-type Schwannian/melanoblastic precursors. The stimulation of human N-type neuroblastoma cell proliferation by normal human bone marrow monocytic cell conditioned medium (BMCM) has been demonstrated in vitro, a finding consistent with the high frequency of bone marrow (BM) metastases in patients with advanced NB. Inorganic arsenic trioxide (As(2)O(3)), already clinically approved for the treatment of several hematological malignancies, is currently under investigation for NB. Recent studies show that As(2)O(3) induces apoptosis in NB cells. We examined the impact of BMCM on growth and survival of As(2)O(3)-treated NB cell lines, to evaluate the response of cultured NB cell variants to regulatory agents. We studied the effect of BMCM on survival and clonogenic growth of eleven As(2)O(3)-treated NB cell lines grown in sparsely seeded, non-adherent, semi-solid cultures. As(2)O(3) had a strong inhibitory effect on survival of all tested NB cell lines. BMCM augmented cell growth and survival and reversed the inhibitory action of As(2)O(3) in all tested cell lines, but most strongly in N-type cells(.) While As(2)O(3) effectively reduced survival of all tested NB cell lines, BMCM effectively impacted its inhibitory action. Better understanding of micro-environmental regulators affecting human NB tumor cell growth and survival may be seminal to the development of therapeutic strategies and clinically effective agents for this condition.
人类神经母细胞瘤（NB）和NB细胞系中存在三种表型不同的细胞类型：I型干细胞、N型成神经细胞前体和S型雪旺氏/成黑素细胞前体。正常人骨髓单核细胞条件培养基（BMCM）对人N型神经母细胞瘤细胞增殖的刺激作用已在体外得到证实，这一发现与晚期NB患者骨髓（BM）转移的高发生率一致。无机三氧化二砷（As(2)O(3)）已被临床批准用于治疗几种血液系统恶性肿瘤，目前正在对NB进行研究。最近的研究表明，As(2)O(3)可诱导NB细胞凋亡。我们研究了BMCM对经As(2)O(3)处理的NB细胞系生长和存活的影响，以评估培养的NB细胞变体对调节因子的反应。我们研究了BMCM对在稀疏接种、非贴壁、半固体培养中生长的11种经As(2)O(3)处理的NB细胞系存活和克隆生长的影响。As(2)O(3)对所有测试的NB细胞系的存活均有强烈的抑制作用。BMCM促进了细胞生长和存活，并逆转了As(2)O(3)在所有测试细胞系中的抑制作用，但在N型细胞中作用最强。虽然As(2)O(3)有效地降低了所有测试NB细胞系的存活率，但BMCM有效地影响了其抑制作用。更好地了解影响人类NB肿瘤细胞生长和存活的微环境调节因子可能对开发针对这种疾病的治疗策略和临床有效药物至关重要。
