Sansom Owen J, Mansergh Fiona C, Evans Martin J, Wilkins Julie A, Clarke Alan R
Beatson Institute of Cancer Research, Glasgow, Scotland, UK.
Gut. 2007 Oct;56(10):1410-4. doi: 10.1136/gut.2006.116921. Epub 2007 Feb 13.
SPARC (secreted protein acidic, rich in cysteine) is a matricellular protein that has been found to be activated in a number of human cancers. More recently, it has been shown to be upregulated in human gastric and colorectal cancer. We therefore wished to address the functional importance of SPARC upregulation to intestinal tumorigenesis in vivo.
SPARC upregulation was determined in intestinal adenomas of tumour-prone Apc(Min/+) mice at both the RNA and the protein level. To determine the functional importance of SPARC for intestinal tumorigenesis we then intercrossed Sparc knockout mice with Apc(Min/+) mice (n = 20). Intestinal enterocyte migration was examined using bromodeoxyuridine labelling studies.
Levels of murine Sparc and several related proteins were upregulated in adenomas arising in Apc(Min/+) mice. A deficiency of Sparc strongly suppressed adenoma formation in Apc(Min/+) mice (p>or=0.0001). Importantly, a deficiency of Sparc also accelerated enterocyte migration (p = 0.01), as perturbed slow epithelial migration may underpin adenoma formation in the intestine.
These data implicate Sparc in both cell migration and tumour formation, and identify Sparc as a potential therapeutic target for colorectal cancer.
SPARC（富含半胱氨酸的酸性分泌蛋白）是一种基质细胞蛋白，已发现在多种人类癌症中被激活。最近，研究表明其在人类胃癌和结直肠癌中上调。因此，我们希望探讨SPARC上调在体内肠道肿瘤发生中的功能重要性。
在易患肿瘤的Apc(Min/+)小鼠的肠道腺瘤中，从RNA和蛋白质水平测定SPARC的上调情况。为了确定SPARC对肠道肿瘤发生的功能重要性，我们将Sparc基因敲除小鼠与Apc(Min/+)小鼠进行杂交（n = 20）。使用溴脱氧尿苷标记研究检测肠道肠上皮细胞迁移情况。
在Apc(Min/+)小鼠产生的腺瘤中，小鼠Sparc及几种相关蛋白的水平上调。Sparc基因缺失强烈抑制了Apc(Min/+)小鼠的腺瘤形成（p≥0.0001）。重要的是，Sparc基因缺失还加速了肠上皮细胞迁移（p = 0.01），因为上皮细胞迁移缓慢可能是肠道腺瘤形成的基础。
这些数据表明Sparc在细胞迁移和肿瘤形成中均起作用，并确定Sparc为结直肠癌的潜在治疗靶点。
