Hypoxia activates enhanced invasive potential and endogenous hyaluronic acid production by glioblastoma cells.
Hypoxia activates enhanced invasive potential and endogenous hyaluronic acid production by glioblastoma cells.
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缺氧激活胶质母细胞瘤细胞增强的侵袭潜力和内源性透明质酸的产生。
DOI：
10.1039/c7bm01195d
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发表时间：
2018-03-26
影响因子：
6.6
通讯作者：
Harley B
中科院分区：
文献类型：
--
作者：
Chen JE ;Lumibao J ;Blazek A ;Gaskins HR ;Harley B
胶质母细胞瘤（GBM）是成人脑癌中最常见、最具侵袭性、最致命的一种，其生存率较短（中位12-15个月，5年以上不到5%）。复杂的肿瘤微环境包括肿瘤边缘的基质转移，如透明质酸（HA）的渐变。此外，由肿瘤氧含量降低引起的代谢应激可能有助于肿瘤的进展。然而，基质成分与代谢应激之间的相互作用尚不清楚。在这项研究中，我们制造了一个体外脑模因ha装饰明胶水凝胶平台，加入可变氧浓度来模拟肿瘤内缺氧。我们观察到，U87 GBM细胞的EGFR状态（野生型与组成型活性EGFRvIII突变体）影响了缺氧和基质结合HA的增殖和代谢活性。侵袭试验表明，在缺氧条件下，两种细胞类型的侵袭均显著增强。此外，我们观察到可溶性HA在GBM细胞侵袭增强的情况下的代偿性分泌，与我们之前使用其他GBM细胞系的发现一致。有趣的是，U87 GBM细胞通过向更无氧的代谢状态转变来适应缺氧，这一机制可能有助于GBM细胞的侵袭。总的来说，这些数据表明，三维水凝胶的使用为研究基质组成和代谢挑战对GBM细胞侵袭的影响提供了一种强大的方法，GBM细胞侵袭是导致最常见、侵袭性和致命的成人脑癌的关键因素。
Glioblastoma (GBM) is the most common, aggressive, and deadly form of adult brain cancer, and is associated with a short survival rate (median 12–15 months, 5+ year less than 5%). The complex tumor microenvironment includes matrix transitions at the tumor margin, such as gradations in hyaluronic acid (HA). In addition, metabolic stress induced by decreased oxygen content across the tumor may contribute to tumor progression. However, cross-talk between matrix composition and metabolic stress remains unclear. In this study, we fabricated an in vitro brain memetic HA-decorated gelatin hydrogel platform incorporating variable oxygen concentrations to mimic intra-tumoral hypoxia. We observed that EGFR status (wildtype vs. a constitutively active EGFRvIII mutant) of U87 GBM cells affected proliferation and metabolic activity in response to hypoxia and matrix-bound HA. The use of an invasion assay revealed that invasion was significantly enhanced in both cell types under hypoxia. Moreover, we observed compensatory secretion of soluble HA in cases of enhanced GBM cell invasion, consistent with our previous findings using other GBM cell lines. Interestingly, U87 GBM cells adapted to hypoxia by shifting toward a more anaerobic metabolic state, a mechanism that may contribute to GBM cell invasion. Collectively, these data demonstrate that the use of a three-dimensional hydrogel provides a robust method to study the impact of matrix composition and metabolic challenges on GBM cell invasion, a key factor contributing to the most common, aggressive, and deadly form of adult brain cancer.
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DOI：
10.1158/1541-7786.mcr-13-0629
发表时间：
2014-10
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Kim Y;Kumar S
通讯作者：
Kumar S
影响因子：
10
作者：
Caliari, Steven R.;Weisgerber, Daniel W.;Grier, William K.;Mahmassani, Ziad;Boppart, Marni D.;Harley, Brendan A. C.
通讯作者：
Harley, Brendan A. C.
DOI：
10.1039/c3ib40170g
发表时间：
2014-06
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Ehsan SM;Welch-Reardon KM;Waterman ML;Hughes CC;George SC
通讯作者：
George SC
影响因子：
3.8
作者：
Heffernan, John M.;Overstreet, Derek J.;Sirianni, Rachael W.
通讯作者：
Sirianni, Rachael W.
影响因子：
14
作者：
Ananthanarayanan, Badriprasad;Kim, Yushan;Kumar, Sanjay
通讯作者：
Kumar, Sanjay