Presence of cancer-associated fibroblasts inversely correlates with Schwannian stroma in neuroblastoma tumors.
Presence of cancer-associated fibroblasts inversely correlates with Schwannian stroma in neuroblastoma tumors.
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DOI：
10.1038/modpathol.2009.52
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发表时间：
2009-07
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基质细胞在调节肿瘤血管生成中起着核心作用。最近的研究表明，间质肌成纤维细胞[癌症相关成纤维细胞]在许多类型的成人癌症中积极促进肿瘤生长和增强肿瘤血管生成。为了评价肿瘤相关成纤维细胞在神经母细胞瘤血管生成中的作用以及它们与基质雪旺细胞的关系，我们对60例原发神经母细胞瘤和一种新的神经母细胞瘤异种移植模型中的肿瘤相关成纤维细胞进行了量化。肿瘤切片检查有无微血管增殖，这是肿瘤血管生成的标志。肿瘤相关成纤维细胞的特征是α-平滑肌肌动蛋白(α-SMA)免疫染色阳性，而与周细胞的区别在于大分子钙调蛋白呈阴性染色。对α-SMA阳性细胞进行定量，当面积的1.0%为阳性时，其数量为高。分析了高肿瘤相关成纤维细胞数量、微血管增殖和已确定的预后因素之间的关系。大量的癌症相关成纤维细胞与Schwannian Stroma差的组织病理学和微血管增殖有关。在46个施万尼间质贫乏的肿瘤中，37个(80%)的肿瘤间质中有大量的癌相关成纤维细胞，而在14个施万尼间质丰富/显性肿瘤中只有2个(14%)(p<；0.001)。有微血管增殖的37个肿瘤中有33个(89%)有较多的肿瘤相关成纤维细胞，而在22个没有微血管增殖的肿瘤中有9个(40%)有较多的肿瘤相关成纤维细胞(p<；0.001)。在有雪旺细胞浸润组(n=10)，肿瘤相关成纤维细胞数/mm~2比无基质雪旺细胞组(n=9)少约7倍(平均分别为51±30vs368±105vs368±105p<；0.001)。因此，与癌症相关的成纤维细胞与雪旺细胞的存在呈负相关，这表明雪旺细胞可能阻止成纤维细胞的激活。更深入地了解肿瘤相关成纤维细胞在神经母细胞瘤血管生成中的作用，可能会指导未来基质导向治疗策略的发展。
Stromal cells play a central role in the regulation of tumor angiogenesis. Recent studies have shown that stromal myofibroblasts [cancer-associated fibroblasts] actively promote tumor growth and enhance tumor angiogenesis in many types of adult carcinomas. To evaluate the role cancer-associated fibroblasts play in neuroblastoma angiogenesis and investigate their relationship to stromal Schwann cells, we quantified cancer-associated fibroblasts in 60 primary neuroblastoma tumors and in a novel neuroblastoma xenograft model in which murine Schwann cells were induced to infiltrate into the tumor stroma. Tumor sections were examined for presence of microvascular proliferation, a hallmark of tumor angiogenesis. Cancer-associated fibroblasts were characterized by positive immunostaining for α-smooth muscle actin (α-SMA) and were distinguished from pericytes by staining negatively for high-molecular weight caldesmon. α-SMA positive cells were quantified and their number was defined as high when >1.0% of the area was positive. Associations between high cancer-associated fibroblast number, microvascular proliferation, and established prognosticators were analyzed. High numbers of cancer-associated fibroblasts were associated with Schwannian Stroma-poor histopathology and microvascular proliferation. Thirty-seven (80%) of the 46 Schwannian Stroma-poor tumors had high numbers of cancer-associated fibroblasts in the tumor stroma compared to only 2 (14%) of the 14 Schwannian Stroma-rich/dominant tumors (p<0.001). Thirty-three (89%) of 37 tumors with microvascular proliferation had high numbers of cancer-associated fibroblasts compared to 9 (40%) of 22 tumors without microvascular proliferation (p <0.001). In the xenografts with infiltrating Schwann cells (n=10), the number of cancer-associated fibroblasts/mm2 was ~7-fold less than in the control xenografts without stromal Schwann cells (n=9) (mean of 51 ± 30 vs 368 ± 105, respectively; p<0.001). Thus, cancer-associated fibroblasts were inversely associated with presence of Schwann cells, suggesting that Schwann cells may prevent the activation of fibroblasts. A deeper understanding of the role cancer-associated fibroblasts play in neuroblastoma angiogenesis may guide future development of stroma-directed therapeutic strategies.
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影响因子：
8
作者：
Chlenski, A.;Guerrero, L. J.;Cohn, S. L.
通讯作者：
Cohn, S. L.
影响因子：
0.7
作者：
Desmoulière, A;Guyot, C;Gabbiani, C
通讯作者：
Gabbiani, C
影响因子：
5.3
作者：
Micke, P;Östman, A
通讯作者：
Östman, A
影响因子：
6
作者：
Liu, SQ;Tian, YF;Cohn, SL
通讯作者：
Cohn, SL
影响因子：
3.4
作者：
Nakayama, H;Miyazaki, E;Enzan, H
通讯作者：
Enzan, H