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

近年来，对肿瘤细胞生长和转移的初始阶段的研究不足，癌症研究的进展越来越多。尤其是肿瘤的侵袭和血管生成是乳腺癌、卵巢癌和胃癌转移的重要环节，也是预后较差的因素。然而，调控整个过程的确切机制仍不清楚，我们假设间质因素参与了CRC的进展，部分是通过侵袭和血管生成因子的产生。[结果]1.在结直肠癌成纤维细胞中检测到MMP2的表达，而在转移性的SW620-S5克隆中不表达，而在结直肠癌细胞和结直肠癌成纤维细胞中仅检测到MMP9的表达。TIMP-1和TIMP-2mRNA在结肠成纤维细胞中的表达高于转移和非转移的SW620克隆。PD-ECGF在所有标本的间质巨噬细胞和成纤维细胞中高水平表达。尤其是PDECGF在癌间质组织及癌周间质组织中均有表达。3.血管生成因子PD-ECGF仅在腺瘤中表达，其中重度不典型增生20例(20%)，腺瘤癌5例(25%)。而非肿瘤性息肉和腺瘤伴低级别不典型增生均为阴性。腺瘤中PD-ECGF的表达强度与Ki-67的表达呈正相关(p&lt；.001)。而PD-ECGF与P53蛋白表达无相关性。[结论]间质细胞在结直肠癌的侵袭和转移中起重要作用。

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.