Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications.
Alterations of gene expression and protein synthesis in co-cultured adipose tissue-derived stem cells and squamous cell-carcinoma cells: consequences for clinical applications.
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DOI：
10.1186/scrt454
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发表时间：
2014-05-12
影响因子：
7.5
通讯作者：
Dexheimer V
中科院分区：
文献类型：
--
作者：
Koellensperger E;Gramley F;Preisner F;Leimer U;Germann G;Dexheimer V
这是第一个评估人类脂肪组织源性干细胞（ADSCs）和人类鳞状细胞癌细胞（SCCs）相互作用的研究，涉及一种前瞻性的基于细胞的皮肤再生疗法，以及由此导致的ADSCs和SCCs的意外共定位。将ADSCs与A431-SCCs和原代SCCs （pSCCs）在transwell系统中共培养，通过评估倍增时间、迁移和侵袭、血管生成、229种肿瘤相关基因的实时定量PCR、20种趋化因子和生长因子以及8种基质金属蛋白酶（MMPS）的多重蛋白检测来分析细胞间的相互作用。将共培养的结果与单独培养的结果进行比较。与A431-SCCs共培养时，ADSCs在板上的增殖显著增加（P = 0.038）。PSCCs和ADSCs在板上共培养时增殖显著降低（P <0.001和P = 0.03）。共培养组pSCC的迁移量显著增加（P = 0.009）， a431 - scc共培养组ADSCs的迁移量显著增加（P = 0.012）。pSCCs和A431-SCCs的侵袭行为在共培养中分别平均增加33%和35% （P = 0.038和P <0.001）。此外，在体外血管生成实验中，共培养ADSC-A431-SCCs和共培养ADSCs-pSCCs的条件培养基诱导了试管形成。在a431 - scc共培养中，ADSCs中有36个基因上调，6个基因下调，A431-SCCs中有14个基因上调，8个基因下调。在pSCC -共培养中，ADSCs中有36个基因上调，2个基因下调，pSCC中有1个基因上调，3个基因下调。蛋白表达分析显示共培养中只产生3种蛋白（CXCL9、IL-1b和MMP-7）。在a431 - scc共培养中，17种蛋白的浓度比单培养ADSCs显著增加（2.8- 357倍），15种蛋白的表达量比单培养A431-SCCs高（2.8- 1527倍）。在pSCC-共培养中，10种蛋白的浓度比adscs -单培养增加（2.5- 77倍），15种蛋白的浓度比pSCC单培养增加（2.6- 480倍）。这是第一项评估原发性人ADSCs与人SCCs可能相互作用的研究，指出无疑会增加肿瘤风险，在考虑将分离的人ADSCs用于皮肤再生治疗的临床应用时，不应忽视这一点。
This is the first study evaluating the interactions of human adipose tissue derived stem cells (ADSCs) and human squamous cell carcinoma cells (SCCs), with regard to a prospective cell-based skin regenerative therapy and a thereby unintended co-localization of ADSCs and SCCs. ADSCs were co-cultured with A431-SCCs and primary SCCs (pSCCs) in a transwell system, and cell-cell interactions were analyzed by assessing doubling time, migration and invasion, angiogenesis, quantitative real time PCR of 229 tumor associated genes, and multiplex protein assays of 20 chemokines and growth factors and eight matrix metalloproteinases (MMPS). Results of co-culture were compared to those of the respective mono-culture. ADSCs’ proliferation on the plate was significantly increased when co-cultured with A431-SCCs (P = 0.038). PSCCs and ADSCs significantly decreased their proliferation in co-culture if cultured on the plate (P <0.001 and P = 0.03). The migration of pSCC was significantly increased in co-culture (P = 0.009), as well as that of ADSCs in A431-SCC-co-culture (P = 0.012). The invasive behavior of pSCCs and A431-SCCs was significantly increased in co-culture by a mean of 33% and 35%, respectively (P = 0.038 and P <0.001). Furthermore, conditioned media from co-cultured ADSC-A431-SCCs and co-cultured ADSCs-pSCCs induced tube formation in an angiogenesis assay in vitro. In A431-SCC-co-culture 36 genes were up- and 6 were down-regulated in ADSCs, in A431-SCCs 14 genes were up- and 8 genes were down-regulated. In pSCCs-co-culture 36 genes were up-regulated in ADSCs, two were down-regulated, one gene was up-regulated in pSCC, and three genes were down-regulated. Protein expression analysis revealed that three proteins were exclusively produced in co-culture (CXCL9, IL-1b, and MMP-7). In A431-SCC-co-culture the concentration of 17 proteins was significantly increased compared to the ADSCs mono-culture (2.8- to 357-fold), and 15 proteins were expressed more highly (2.8- to 1,527-fold) compared to the A431-SCCs mono-culture. In pSCC-co-culture the concentration of 10 proteins was increased compared to ADSCs-mono-culture (2.5- to 77-fold) and that of 15 proteins was increased compared to pSCC mono-culture (2.6- to 480-fold). This is the first study evaluating the possible interactions of primary human ADSCs with human SCCs, pointing towards a doubtlessly increased oncological risk, which should not be neglected when considering a clinical use of isolated human ADSCs in skin regenerative therapies.
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影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
6
作者：
Bekes, Erin M.;Schweighofer, Bernhard;Deryugina, Elena I.
通讯作者：
Deryugina, Elena I.
影响因子：
2.6
作者：
Eisma, RJ;Spiro, JD;Kreutzer, DL
通讯作者：
Kreutzer, DL
影响因子：
4.2
作者：
Cho, Yong Beom;Lee, Woo Yong;Lee, Kuhn Uk
通讯作者：
Lee, Kuhn Uk
DOI：
10.5402/2012/546927
发表时间：
2012
期刊：
ISRN oncology
影响因子：
--
作者：
Dewing D;Emmett M;Pritchard Jones R
通讯作者：
Pritchard Jones R