Stromal Integrin α11β1 Affects RM11 Prostate and 4T1 Breast Xenograft Tumors Differently.
Stromal Integrin α11β1 Affects RM11 Prostate and 4T1 Breast Xenograft Tumors Differently.
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DOI：
10.1371/journal.pone.0151663
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Stuhr L
中科院分区：
文献类型：
--
作者：
Reigstad I;Smeland HY;Skogstrand T;Sortland K;Schmid MC;Reed RK;Stuhr L
已暗示胶原结合整合素α11β1在癌发生中起作用。由于对基质整合素α11β1如何影响肿瘤发展的不同方面仍知之甚少，我们希望使用体内SCID整合素α11缺陷小鼠模型，在小鼠4 T1乳腺和RM 11前列腺肿瘤中检查对原发性肿瘤生长、纤维化、肿瘤间质液压力（PIF）和转移的直接影响。使用卡尺测量肿瘤生长，通过针芯技术测量PIF，通过α-SMA免疫荧光染色测量活化的成纤维细胞，通过透射电子显微镜和苦味酸天狼星红染色测量纤维化。使用苏木精和伊红染色切片评价转移。与SCID整联蛋白α11野生型（WT）小鼠相比，SCID整联蛋白α11缺陷型（α11-KO）小鼠中RM 11肿瘤生长显着减少，而在4 T1肿瘤模型中没有类似的效果。与WT相比，4 T1模型显示整合素α11-KO小鼠的胶原纤维直径发生变化，而在RM 11模型中未发现。与WT小鼠相比，整合素α11缺陷小鼠肿瘤中活化成纤维细胞的量、总胶原含量、胶原组织或PIF无显著差异。两组之间的肺转移也没有差异。基质整合素α11β1缺乏对肿瘤生长和胶原纤维直径的影响取决于肿瘤类型，但对肿瘤PIF或肺转移的发展没有影响。
It has been implied that the collagen binding integrin α11β1 plays a role in carcinogenesis. As still relatively little is known about how the stromal integrin α11β1 affects different aspects of tumor development, we wanted to examine the direct effects on primary tumor growth, fibrosis, tumor interstitial fluid pressure (PIF) and metastasis in murine 4T1 mammary and RM11 prostate tumors, using an in vivo SCID integrin α11-deficient mouse model. Tumor growth was measured using a caliper, PIF by the wick-in-needle technique, activated fibroblasts by α-SMA immunofluorescence staining and fibrosis by transmission electron microscopy and picrosirius-red staining. Metastases were evaluated using hematoxylin and eosin stained sections. RM11 tumor growth was significantly reduced in the SCID integrin α11-deficient (α11-KO) compared to in SCID integrin α11 wild type (WT) mice, whereas there was no similar effect in the 4T1 tumor model. The 4T1 model demonstrated an alteration in collagen fibril diameter in the integrin α11-KO mice compared to WT, which was not found in the RM11 model. There were no significant differences in the amount of activated fibroblasts, total collagen content, collagen organization or PIF in the tumors in integrin α11-deficient mice compared to WT mice. There was also no difference in lung metastases between the two groups. Deficiency of stromal integrin α11β1 showed different effects on tumor growth and collagen fibril diameter depending on tumor type, but no effect on tumor PIF or development of lung metastasis.