Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stroma
Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stroma
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DOI：
10.1002/ijc.20969
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发表时间：
2005-07-20
影响因子：
6.4
通讯作者：
Ochiai, A
中科院分区：
文献类型：
--
作者：
Sangai, T;Ishii, G;Ochiai, A
众所周知，癌症-基质相互作用在癌症进展过程中发挥重要作用。最近，我们已经证明，骨髓来源的血管内皮细胞（BMD-VE）和肌成纤维细胞（BMD-MF）招募到人胰腺癌细胞系Capan-1诱导的基质。为了评估癌细胞类型的差异对BMD-VE和BMD-MF募集的影响，将10种人癌细胞系植入移植有双突变小鼠（RAG-1-/-β-gal Tg或RAG-1-/-GFP Tg）骨髓的免疫缺陷小鼠的皮下组织中。测量BMD-VE（% BMD-VE）和BMD-MF（% BMD-MF）的募集频率以及肿瘤相关参数[肿瘤体积（TV）、微血管密度（MVD）和间质比例（% St）]。分析了它们之间的相关性。尽管% BMD-VE和% BMD-MF变化（分别为0 - 21.6%，0 - 29.6%），但取决于癌细胞系，两个参数均与% St显著相关（p <0.005）。此外，% BMD-VE和% BMD-MF也显著相关（p <0.005）。为了评估肿瘤生长部位对募集或目标细胞的影响，将人胰腺癌细胞系Capan-1移植到5个不同部位：皮下组织、腹膜、肝、脾和肺。皮下和腹膜肿瘤诱导结缔组织增生性间质（% St分别为22.7%、19.5%），并含有BMD-VE（% BMD-VE = 21.6%，16.5%）和BMD-MF（% BMD-MF分别为29.6%，24.5%），但在肝脏的肿瘤中观察到弱的基质诱导，没有BMD-VE或-MF的募集，脾和肺（% St = 9.7%）。百分之九点一5.4%）。cDNA微阵列分析确定了29个基因的表达，特别是上调或下调的细胞系，诱导丰富的基质反应。然而，它们不编码直接参与基质细胞募集（趋化因子）、分化（细胞因子）或增殖（生长因子）的分子。这些结果表明，BMD-VE和-MF的募集是癌症进展期间基质形成所需的，并且癌症微环境在基质反应和BMD-VE和-MF的募集中是重要的。(c)2005年威利-利斯。Inc.
Cancer-stromal interaction is well known to play important roles during cancer progression. Recently we have demonstrated that bone marrow-derived vascular endothelial cells (BMD-VE) and myofibroblasts (BMD-MF) are recruited into the human pancreatic cancer cell line Capan-1 induced stroma. To assess the effect of the difference in cancer cell types on the recruitment of BMD-VE and BMD-MF, 10 kinds of human cancer cell line were implanted into the subctaneous tissue of the immunodeficient mice transplanted with bone marrow of double-mutant mice (RAG-1-/- beta-gal Tg or RAG-1-/- GFP Tg). The recruitment frequency of BMD-VE (%BMD-VE) and BMD-MF (%BMD-MF), and tumor-associated parameters [tumor volume (TV), microvessel density (MVD) and stromal proportion (%St)] were measured. The correlation among them was analyzed. Although %BMD-VE and %BMD-MF varied (from 0 to 21.6%, 0 to 29.6%, respectively), depending on the cancer cell line, both parameters were significantly correlated with %St (p < 0.005). Furthermore %BMD-VE and %BMD-MF also significantly correlated (p < 0.005). In order to assess the effect of tumor growth sites on the recruitment or the cells of interest, a human pancreatic cancer cell line, Capan-1, was transplanted into 5 different sites: subcutaneous tissue, peritoneum, liver, spleen and lung. Tumors in the subcutaneous tissue and peritoneum induced desmoplastic stroma (%St = 22.7%, 19.5%, respectively) and contained BMD-VE (%BMD-VE = 21.6%, 16.5% respectively) and BMD-MF (%BMD-MF = 29.6%, 24.5%, respectively), but weak stromal induction without recruitment of BMD-VE or -MF was observed in the tumors at of the liver, spleen and lung (%St = 9.7%. 9.1%. 5.4%, respectively). cDNA microarray analysis identified the 29 genes that expression was especially up or down-regulated in the cell line that induced an abundant stromal reaction. However they did not encoded the molecules that were directly involved in stromal cell recruitment (chemokines), differentiation (cytokines) or proliferation (growth factors). These results indicate that the recruitment of BMD-VE and -MF is required for stromal formation during cancer progression and that the cancer microenvironment is important in stromal reaction and the recruitment of BMD-VE and -MF. (c) 2005 Wiley-Liss. Inc.