Suppression and activation of the malignant phenotype by extracellular matrix in xenograft models of bladder cancer: a model for tumor cell "dormancy".
Suppression and activation of the malignant phenotype by extracellular matrix in xenograft models of bladder cancer: a model for tumor cell "dormancy".
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膀胱癌异种移植模型中细胞外基质对恶性表型的抑制和激活：肿瘤细胞“休眠”模型。
DOI：
10.1371/journal.pone.0064181
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ihnat MA
中科院分区：
文献类型：
--
作者：
Hurst RE;Hauser PJ;Kyker KD;Heinlen JE;Hodde JP;Hiles MC;Kosanke SD;Dozmorov M;Ihnat MA
A major problem in cancer research is the lack of a tractable model for delayed metastasis. Herein we show that cancer cells suppressed by SISgel, a gel-forming normal ECM material derived from Small Intestine Submucosa (SIS), in flank xenografts show properties of suppression and re-activation that are very similar to normal delayed metastasis and suggest these suppressed cells can serve as a novel model for developing therapeutics to target micrometastases or suppressed cancer cells. Co-injection with SISgel suppressed the malignant phenotype of highly invasive J82 bladder cancer cells and highly metastatic JB-V bladder cancer cells in nude mouse flank xenografts. Cells could remain viable up to 120 days without forming tumors and appeared much more highly differentiated and less atypical than tumors from cells co-injected with Matrigel. In 40% of SISgel xenografts, growth resumed in the malignant phenotype after a period of suppression or dormancy for at least 30 days and was more likely with implantation of 3 million or more cells. Ordinary Type I collagen did not suppress malignant growth, and tumors developed about as well with collagen as with Matrigel. A clear signal in gene expression over different cell lines was not seen by transcriptome microarray analysis, but in contrast, Reverse Phase Protein Analysis of 250 proteins across 4 cell lines identified Integrin Linked Kinase (ILK) signaling that was functionally confirmed by an ILK inhibitor. We suggest that cancer cells suppressed on SISgel could serve as a model for dormancy and re-awakening to allow for the identification of therapeutic targets for treating micrometastases.
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影响因子：
11.2
作者：
Barkan D;Kleinman H;Simmons JL;Asmussen H;Kamaraju AK;Hoenorhoff MJ;Liu ZY;Costes SV;Cho EH;Lockett S;Khanna C;Chambers AF;Green JE
通讯作者：
Green JE
影响因子：
11.5
作者：
Milojkovic, Dragana;Apperley, Jane
通讯作者：
Apperley, Jane
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
6.6
作者：
DINNEY, CPN;FISHBECK, R;KILLION, JJ
通讯作者：
KILLION, JJ
影响因子：
2.8
作者：
Hoffman, Robert M.
通讯作者：
Hoffman, Robert M.