Role of I-TAC-binding receptors CXCR3 and CXCR7 in proliferation, activation of intracellular signaling pathways and migration of various tumor cell lines
Role of I-TAC-binding receptors CXCR3 and CXCR7 in proliferation, activation of intracellular signaling pathways and migration of various tumor cell lines
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DOI：
10.2478/v10042-008-0091-7
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发表时间：
2010-01-01
影响因子：
1.5
通讯作者：
Majka, Marcin
中科院分区：
文献类型：
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作者：
Miekus, Katarzyna;Jarocha, Danuta;Majka, Marcin
趋化因子及其受体刺激肿瘤生长、迁移和侵袭。在这项研究中，我们评估了CXCR3和CXCR7受体在宫颈癌、横纹肌肉瘤和胶质母细胞瘤细胞系中的表达和功能。我们发现这两种受体在肿瘤细胞中有不同程度的表达。所有肿瘤细胞系均以mRNA和蛋白水平表达CXCR7。CXCR7的表达在横纹肌肉瘤亚型之间存在差异。该受体在肺泡型横纹肌肉瘤中高表达，在胚胎型横纹肌肉瘤中低表达。CXCR3在大多数肿瘤细胞系中表达较低。在I-TAC刺激下，AKT和MAPK激酶被激活。然而，激活促生长途径并没有增加肿瘤细胞的增殖速率。由于趋化因子刺激各种细胞类型的迁移，因此研究了I-TAC刺激肿瘤细胞迁移的能力。我们没有单独观察肿瘤细胞向I-TAC梯度的迁移。然而，在低剂量下，I-TAC使肿瘤细胞对SDF-1 β梯度增敏，并与SDF-1 β协同激活细胞内通路。我们的数据表明，I-TAC及其受体在实体肿瘤生物学中的重要作用，我们假设I-TAC结合受体可能被用作抗肿瘤治疗的潜在靶点。
Chemokines and its receptors stimulate tumor growth, migration and invasion. In this study we evaluated the expression and function of CXCR3 and CXCR7 receptors in cervical carcinoma, rhabdomyosarcoma and glioblastoma cell lines. We found that both receptors were expressed at different degree by tumor cells. CXCR7 was expressed at both mRNA and protein level by all tumor cell lines. The expression of CXCR7 differed between rhabdomyosarcoma subtypes. The receptor was highly expressed in alveolar rhabdomyosarcoma and the expression was low in embryonal rhabdomyosarcoma. The expression of CXCR3 was low in majority of the tumor cell lines. Upon I-TAC stimulation AKT and MAPK kinases were activated. However, the activation of growth promoting pathways did not increased the proliferation rate of tumor cells. Since chemokines stimulate the migration of various cell types the ability of I-TAC to stimulate migration of tumor cells were studied. We did not observe the migration of tumor cells toward I-TAC gradient alone. However, at the low dose, I-TAC sensitized tumor cells toward SDF-1 beta gradient and synergized with SDF-1 beta in activation of intracellular pathways. Our data suggest an important role of I-TAC and its receptors in biology of solid tumors and we postulate that I-TAC-binding receptors might be used as the potential targets for antitumor therapy.