Gupta Vivekanand, Singh Sukh Mahendra
School of Biotechnology, Banaras Hindu University, Varanasi 221005, India.
J Reprod Immunol. 2007 Jun;74(1-2):90-102. doi: 10.1016/j.jri.2007.01.003. Epub 2007 Feb 2.
Little information is available regarding the existence of gender dimorphism of tumor growth for most types of tumors. In a previous report we have demonstrated the existence of gender dimorphism in the growth of a murine T cell lymphoma, designated as Dalton's lymphoma (DL); moreover, tumor-associated macrophages (TAM) were found to play a central role in the manifestation of gender dimorphism observed in the growth of this T cell lymphoma. In view of these observations, the present investigation was undertaken to study if gender dimorphism in the growth of a T cell tumor also could be associated with a gender-dependent differential myelopoiesis of bone marrow cells. We have demonstrated the existence of a gender dimorphism in the proliferation, apoptosis and myeloid differentiation of bone marrow cells obtained from male and female tumor-bearing hosts. Androgen and estrogen were found to alter directly the growth properties of bone marrow cells, as also determined by the use of receptor antagonists of these hormones, flutamide and tamoxifen. Bone marrow cells of male and female tumor-bearing hosts also showed a differential expression of the cell cycle and apoptosis regulatory protein p53 and macrophage-colony stimulating factor (M-CSF) genes. Bone marrow cells of male tumor-bearing hosts showed a predominant differentiation in the macrophage lineage whereas those of female tumor-bearing mice were in the granulocyte lineage. Bone marrow-derived macrophages (BMDM) from male and female tumor-bearing mice also showed the existence of gender dimorphism with respect to their differentiation and activation. These observations are of clinical significance with respect to understanding of the host-tumor relationship at the level of gender dimorphism of myelopoiesis.
对于大多数类型的肿瘤,关于肿瘤生长的性别二态性存在的信息很少。在之前的一份报告中,我们已经证明了一种小鼠T细胞淋巴瘤(称为道尔顿淋巴瘤,DL)生长中存在性别二态性;此外,发现肿瘤相关巨噬细胞(TAM)在这种T细胞淋巴瘤生长中观察到的性别二态性表现中起核心作用。鉴于这些观察结果,本研究旨在探讨T细胞肿瘤生长中的性别二态性是否也可能与骨髓细胞的性别依赖性差异骨髓生成有关。我们已经证明了从雄性和雌性荷瘤宿主获得的骨髓细胞在增殖、凋亡和髓系分化方面存在性别二态性。还发现雄激素和雌激素直接改变骨髓细胞的生长特性,这也通过使用这些激素的受体拮抗剂氟他胺和他莫昔芬来确定。雄性和雌性荷瘤宿主的骨髓细胞在细胞周期和凋亡调节蛋白p53以及巨噬细胞集落刺激因子(M-CSF)基因的表达上也存在差异。雄性荷瘤宿主的骨髓细胞在巨噬细胞谱系中表现出主要分化,而雌性荷瘤小鼠的骨髓细胞则在粒细胞谱系中分化。来自雄性和雌性荷瘤小鼠的骨髓源性巨噬细胞(BMDM)在其分化和激活方面也表现出性别二态性。这些观察结果对于在骨髓生成的性别二态性水平上理解宿主-肿瘤关系具有临床意义。