Hypoxia-induced autophagic response is associated with aggressive phenotype and elevated incidence of metastasis in orthotopic immunocompetent murine models of head and neck squamous cell carcinomas (HNSCC).
Hypoxia-induced autophagic response is associated with aggressive phenotype and elevated incidence of metastasis in orthotopic immunocompetent murine models of head and neck squamous cell carcinomas (HNSCC).
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DOI：
10.1016/j.yexmp.2010.11.011
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发表时间：
2011-04
影响因子：
3.6
通讯作者：
Zacharias, Wolfgang
中科院分区：
文献类型：
--
作者：
Vigneswaran, Nadarajah;Wu, Jean;Song, Anren;Annapragada, Ananth;Zacharias, Wolfgang
关键词：
低氧可抵抗放化疗并促进头颈部鳞状细胞癌(HNSCC)的转移。我们利用免疫活性的小鼠HNSCC模型研究了低氧对肿瘤表型的影响。BALB/c小鼠经口注射小鼠鳞状细胞癌细胞LY-2和B4B8。用免疫组织化学方法检测低氧探针匹莫硝唑和碳酸酐酶IX(CAIX)来评价瘤内低氧分数。用免疫组织化学方法检测缺氧区肿瘤细胞的凋亡和自噬。用CoCl2处理体外培养的LY2细胞，检测缺氧诱导的细胞凋亡和自噬反应。B4B8肿瘤呈非侵袭性表型，生长速度慢，无转移扩散。LY2肿瘤表现为侵袭性表型，生长速度快，有局部和远处转移。B4B8肿瘤的瘤内缺氧分数明显低于LY2肿瘤。B4B8肿瘤缺氧区细胞凋亡率高于LY2肿瘤。相比之下，LY2肿瘤中的缺氧区显示出自噬。体外低氧诱导LY2细胞自噬，但不诱导细胞凋亡。在免疫活性的小鼠HNSCC模型中，自噬的诱导和缺氧区细胞凋亡的阻断促进了肿瘤细胞的存活并赋予了侵袭性表型。
Hypoxia confers resistance to chemoradiation therapy and promotes metastasis in head and neck squamous cell carcinomas (HNSCC). We investigated the effects of hypoxia in tumor phenotype using immunocompetent murine HNSCC models. Balb/c mice were injected intraorally with murine squamous cell carcinoma cells LY-2 and B4B8. Intratumoral hypoxia fraction was evaluated by the immunohistochemical detection of hypoxic probe pimonidazole and carbonic anhydrase IX (CAIX). Tumor cell apoptosis and autophagy in hypoxic areas of these tumors were examined immunohistochemially. Hypoxia-induced apoptotic and autophagic responses in vitro were examined by treating LY2 cells with CoCl2. B4B8 tumors exhibited a non-aggressive phenotype characterized by its slow growth rate and the lack of metastatic spread. LY2 tumors demonstrated an aggressive phenotype characterized by rapid growth rate with regional and distant metastasis. Intratumoral hypoxia fraction in B4B8 tumors was significantly lower than LY2 tumors. Hypoxic areas in B4B8 tumors exhibited increased apoptosis rate than LY2 tumors. In contrast, hypoxic areas in LY2 tumors revealed autophagy. Induction of hypoxia in vitro elicited autophagy and not apoptosis in LY2 cells. Induction of autophagy coupled with blockage of apoptosis in hypoxic areas promotes tumor cells survival and confers aggressive phenotype in immunocompetent murine HNSCC models.
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影响因子：
5.3
作者：
Goda, N;Ryan, HE;Johnson, RS
通讯作者：
Johnson, RS
影响因子：
13.3
作者：
Dalby KN;Tekedereli I;Lopez-Berestein G;Ozpolat B
通讯作者：
Ozpolat B
影响因子：
45.3
作者：
Eisbruch, A;Shewach, DS;Lawrence, TS
通讯作者：
Lawrence, TS
影响因子：
8.8
作者：
Bozec, A.;Sudaka, A.;Fischel, J-L;Brunstein, M-C;Etienne-Grimaldi, M-C;Milano, G.
通讯作者：
Milano, G.
影响因子：
3.4
作者：
DINESMAN, A;HAUGHEY, B;VONHOFF, DD
通讯作者：
VONHOFF, DD