Analysis for the role of stromal cells in colorectal cancer invasion and metastasis

近年来，随着对癌细胞生长和转移的初步研究，肿瘤研究的进展越来越多。尤其是肿瘤浸润和血管生成是乳腺癌、卵巢癌和胃癌转移的重要环节，也是影响预后的重要因素。然而，调控这一整体过程的确切机制仍不清楚，我们推测，基质因子参与了CRC的进展，部分是通过侵袭和血管生成因子的产生。这些研究的目的是确定转移性CRC中这些因子的产生是基质细胞还是肿瘤起源，并评估特定血管生成因子在结直肠癌发生中的作用。[结果] 1. MMP-2 mRNA在结肠成纤维细胞中检测到表达，并且在转移性SW 620-S5克隆中不表达，而MMP-9在CRC细胞和结肠成纤维细胞中独特地不表达。相对于转移性和非转移性SW 620克隆，在结肠成纤维细胞中观察到TIMP-1和TIMP-2 mRNA表达的丰度2。PD-ECGF在所有标本的间质巨噬细胞和成纤维细胞中均呈高水平表达。PDECGF在癌间质及癌旁间质中表达尤为明显。3.血管生成因子PD-ECGF仅在腺瘤中显著表达，其中20例重度异型增生中有4例（20%），腺瘤中20例癌中有5例（25%）。而非肿瘤性息肉和腺瘤伴低度异型增生则为阴性。腺瘤中PD-ECGF的强度与Ki-67表达相关（p<0.001）。而PD-ECGF与p53蛋白表达无相关性。VEGF未检测到任何息肉。[结论]间质细胞在结直肠癌侵袭转移中起重要作用。

Recent progress in cancer research is increasing on understudy of the initial step of cancer cell growth and metastasis. Especially tumor invasion and angiogenesis are the important steps for metastasis as well as the poor prognostic factors in breast, ovarian and gastric cancer. However the precise mechanism regulating this overall process remains unclear We hypothesize that stromal factors are involved in CRC progression, in part, though invasion and angiogenic factor production. The purpose of these studies were to determine whether the production of these factors within metastatic CRC is stromal cells or neoplastic in origin and to assess the role of specific angiogenic factor through colorectal carcinogenesis.【Results】 1. MMP-2 mRNA expression was detected in colonic fibroblast and were absent from metastatic SW620-S5 clone, while MMP-9 was uniquely absent from CRC cells and colonic fibroblasts. An abundance of TIMP-1 and -2 mRNA expression was noted in colonic fibroblast relative to metastatic and nonmetastatic SW620 clones 2. PD-ECGF was expressed at high kevels in stromal macrophagesand fibroblasts in all specimens. Especially PDECGF expression was located in cancer stromal tissue as well as cancer surrounding stroma. 3. Angiogenic factor, PD-ECGF, significantly expressed only in adenoma with four of the 20 severe dysplasia (20%) and five of the 20 carcinoma in adenomas (25%). However negative in nonneoplastic polyps and adenoma with low grade dysplasia. The intensity of PD-ECGF in adenoma correlated with Ki-67 expression (p< .001). In contrast PD-ECGF did not correlate with p53 protein. VEGF could not detect any polyps.【Conclusions】 Our results emphasize the importance of stromal cells in CRC invasion and metastasis.