HAb18G/CD147 cell-cell contacts confer resistance of a HEK293 subpopulation to anoikis in an E-cadherin-dependent manner.
HAb18G/CD147 cell-cell contacts confer resistance of a HEK293 subpopulation to anoikis in an E-cadherin-dependent manner.
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DOI：
10.1186/1471-2121-11-27
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发表时间：
2010-04-17
期刊：
影响因子：
--
通讯作者：
Chen ZN
中科院分区：
文献类型：
--
作者：
Ma XK;Wang L;Li Y;Yang XM;Zhao P;HaoTang;Zhu P;Li L;Chen ZN
获得对“anoikis”的抗性有助于细胞在独立基质缺乏条件下的存活，例如肿瘤进展中的细胞和用于生物医学工程的悬浮培养细胞的生产。有证据表明，CD147是一种与肿瘤转移和细胞间接触中细胞存活相关的粘附分子，在抗肿瘤过程中起重要作用。然而，关于CD147在介导细胞-细胞接触和抗氧化中的功能的信息仍然有限，甚至是自相矛盾的。从嗜酸敏感亲代人胚胎肾293细胞衍生的嗜酸抗克隆（HEK293ar），通过形成细胞间接触在嗜酸中存活。HAb18G/CD147 （CD147家族成员）的表达上调，该蛋白位于细胞-细胞连接处。悬浮HEK293ar细胞中HAb18G/CD147的上调通过介导细胞间粘附的形成来抑制anoikis。HEK293ar细胞的Anoikis耐药也需要e -cadherin介导的细胞-细胞接触。HAb18G/CD147和E-cadherin的敲低分别抑制了细胞间接触的形成和增加了anoikis的敏感性。下调HAb18G/CD147后，HEK293ar细胞中E-cadherin的表达明显受到抑制；然而，用E-cadherin siRNA敲低E-cadherin或用特异性抗体和EDTA阻断E-cadherin的结合活性对HAb18G/CD147的表达没有显著影响。最后，用磷酸肌苷3-激酶（PI3K/AKT）抑制剂LY294002预处理，细胞间接触被破坏，细胞数量减少，但用细胞外信号调节激酶（ERK）抑制剂PD98059处理的细胞则没有这种情况。我们的研究结果提供了新的证据，证明HAb18G/ cd147介导的细胞-细胞接触以e -钙粘蛋白依赖的方式赋予anoikis抗性；在高度相关的细胞模型（HEK293ar）中，细胞接触介导的对anoikis的抗性涉及PI3K途径。了解HAb18G/CD147细胞-细胞接触在anoikis抗性中的作用可能有助于理解非锚定生长细胞的存活，例如用于生物医学工程的肿瘤转移和悬浮培养细胞。我们的结果也有助于更好地理解HEK293细胞球体的生物学，HEK293细胞球体是生产人类治疗剂和病毒疫苗的主要主力。
Acquisition of resistance to "anoikis" facilitates the survival of cells under independent matrix-deficient conditions, such as cells in tumor progression and the production of suspension culture cells for biomedical engineering. There is evidence suggesting that CD147, an adhesion molecule associated with survival of cells in tumor metastasis and cell-cell contacts, plays an important role in resistance to anoikis. However, information regarding the functions of CD147 in mediating cell-cell contacts and anoikis-resistance remains limited and even self-contradictory. An anoikis-resistant clone (HEK293ar), derived from anoikis-sensitive parental Human Embryonic Kidney 293 cells, survived anoikis by the formation of cell-cell contacts. The expression of HAb18G/CD147 (a member of the CD147 family) was upregulated and the protein was located at cell-cell junctions. Upregulation of HAb18G/CD147 in suspended HEK293ar cells suppressed anoikis by mediating the formation of cell-cell adhesions. Anoikis resistance in HEK293ar cells also required E-cadherin-mediated cell-cell contacts. Knock-down of HAb18G/CD147 and E-cadherin inhibited cell-cell contacts formation and increased anoikis sensitivity respectively. When HAb18G/CD147 was downregulated, E-cadherin expression in HEK293ar cells was significantly suppressed; however, knockdown of E-cadherin by E-cadherin siRNA or blocking of E-cadherin binding activity with a specific antibody and EDTA had no significant effect on HAb18G/CD147 expression. Finally, pretreatment with LY294002, a phosphoinositide 3-kinase (PI3K/AKT) inhibitor, disrupted cell-cell contacts and decreased cell number, but this was not the case in cells treated with the extracellular signal-regulated kinase (ERK) inhibitor PD98059. Our results provide new evidence that HAb18G/CD147-mediated cell-cell contact confers anoikis resistance in an E-cadherin-dependent manner; and cell-cell contact mediated resistance to anoikis implicates PI3K pathway in a highly relevant cell model (HEK293ar). Understanding of the role of HAb18G/CD147 cell-cell contacts in anoikis resistance may help in understanding the survival of cells in anchorage-independent growth, such as cells in tumor metastasis and suspension culture produced for biomedical engineering. Our results also contribute to a better understanding of the biology of HEK293 cell spheroids, a major workhorse for producing human therapeutic agents and viral vaccines.
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DOI：
10.1152/ajprenal.2000.278.5.f758
发表时间：
2000-05-01
影响因子：
4.2
作者：
Bergin, E;Levine, JS;Lieberthal, W
通讯作者：
Lieberthal, W
影响因子：
20.3
作者：
Cho, JY;Fox, DA;Chain, B
通讯作者：
Chain, B
影响因子：
4.8
作者：
Yang, JM;O'Neill, P;Hait, WN
通讯作者：
Hait, WN
影响因子：
4.8
作者：
Kupferman, Michael E.;Patel, Vyomesh;Myers, Jeffrey N.
通讯作者：
Myers, Jeffrey N.
影响因子：
5.2
作者：
Xu, Jing;Xu, Hui-Yun;Chen, Zhi-Nan
通讯作者：
Chen, Zhi-Nan