Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma
Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma
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DOI：
10.1038/sj.onc.1208635
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发表时间：
2005-06-01
期刊：
影响因子：
8
通讯作者：
Grandis, JR
中科院分区：
文献类型：
--
作者：
Lai, SY;Childs, EE;Grandis, JR
促红细胞生成素（EPO）最初被表征为红细胞的生长因子，用于治疗接受放射疗法和化学疗法的癌症患者的贫血和疲劳。EPO和EPO受体（EPOR）在非造血细胞和癌症中表达。然而，EPO和EPOR在非造血癌细胞中的作用仍然不完全清楚。虽然最近的临床试验表明，在头部和颈部癌症患者接受EPO治疗的肿瘤控制和生存率较差，但EPO和EPOR在头部和颈部鳞状细胞癌（HNSCC）中的作用尚未得到研究。在本研究中，我们证明了以前未被认识的EPO介导的HNSCC细胞通过Janus激酶（JAK）-信号转导和转录激活因子（STAT）信号通路的入侵。此外，我们证实了EPO和EPOR在一组人HNSCC细胞系和组织标本中的表达。EPO的药理学剂量在这些细胞系中也具有有限的增殖作用。这些结果德。新的EPO在介导肿瘤细胞侵袭中的作用。与来自HNSCC患者的原发性肿瘤相比，淋巴结转移灶中EPO和EPOR的水平增加进一步支持EPO/EPOR在HNSCC疾病进展和转移中的作用。
Originally characterized as a growth factor for erythrocytes, erythropoietin (EPO) is used to treat anemia and fatigue in cancer patients receiving radiation therapy and chemotherapy. EPO and the EPO receptor (EPOR) are expressed in nonhematopoietic cells and cancers. However, the role of EPO and EPOR within nonhematopoietic cancer cells remains incompletely understood. Although a recent clinical trial demonstrated worse tumor control and survival in head and neck cancer patients treated with EPO, the role of EPO and EPOR in head and neck squamous cell carcinoma (HNSCC) has not been examined. In the present study, we demonstrate the previously unrecognized EPO-mediated invasion by HNSCC cells through the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Furthermore, we confirmed the expression of EPO and EPOR in a panel of human HNSCC cell lines and tissue specimens. Pharmacological doses of EPO also had a limited proliferation effect in these cell lines. These results de. ne a novel role for EPO in mediating tumor cell invasion. Increased levels of EPO and EPOR in lymph node metastases as compared to primary tumors from HNSCC patients further support the role of EPO/EPOR in HNSCC disease progression and metastasis.