Schor A M, Rushton G, Ferguson J E, Howell A, Redford J, Schor S L
CRC Department of Medical Oncology, Christie Hospital NHS Trust, UK.
Int J Cancer. 1994 Oct 1;59(1):25-32. doi: 10.1002/ijc.2910590107.
Histologically normal breast tissue was obtained from women undergoing surgery for benign breast lesions (n = 12) and mammary carcinomas (n = 15). Four fibroblast subpopulations (FI, FII, FIII and FIV) were isolated from these specimens by differential digestion and centrifugation. FI cells were the first to be released from the tissue digest and consequently assumed to be derived from the interlobular stroma; FIV fibroblasts were tightly associated with the epithelial organoids and are therefore believed to be of intralobular origin. These cells were characterised in terms of their migratory phenotype (classified as either foetal- or adult-like) and the production of motility factors according to previously described techniques. FI fibroblasts obtained from patients with benign breast lesions displayed a foetal migratory phenotype (10/11) and secreted detectable quantities of motility factors (11/11). In contrast, none of the FIV fibroblasts (0/10) obtained from these same patients displayed a foetal-like migratory phenotype or secreted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foetal-like migratory phenotype and secreted motility factors. Fibroblasts were also derived from skin (n = 12) and breast fat tissue (n = 4) of certain patients. In agreement with our previously published observations, skin fibroblasts obtained from non-cancer and cancer patients also differed in terms of their migratory behaviour: none of the skin fibroblast lines (0/5) obtained from non-cancer patients were foetal-like, compared to 3/7 lines from cancer patients. All fat-derived fibroblasts (1 non-cancer and 3 cancer patients) were also foetal-like. Our results indicate (i) functional heterogeneity between FI and FIV fibroblasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal-like) FIV fibroblasts in histologically normal breast tissue adjacent to a carcinoma.
从接受良性乳腺病变手术的女性（n = 12）和乳腺癌患者（n = 15）中获取组织学正常的乳腺组织。通过差异消化和离心从这些标本中分离出四个成纤维细胞亚群（FI、FII、FIII和FIV）。FI细胞是最早从组织消化物中释放出来的，因此被认为源自小叶间基质；FIV成纤维细胞与上皮类器官紧密相关，因此被认为源自小叶内。根据先前描述的技术，这些细胞根据其迁移表型（分为胎儿样或成人样）和运动因子的产生进行表征。从良性乳腺病变患者获得的FI成纤维细胞表现出胎儿迁移表型（10/11），并分泌可检测量的运动因子（11/11）。相比之下，从这些相同患者获得的FIV成纤维细胞中，没有一个表现出胎儿样迁移表型或分泌运动因子（0/10）。在从癌症患者获得的成纤维细胞中，FI（13/13）和FIV（13/13）成纤维细胞均表现出胎儿样迁移表型并分泌运动因子。成纤维细胞也来源于某些患者的皮肤（n = 12）和乳腺脂肪组织（n = 4）。与我们先前发表的观察结果一致，从非癌症和癌症患者获得的皮肤成纤维细胞在迁移行为方面也存在差异：从非癌症患者获得的皮肤成纤维细胞系中没有一个是胎儿样的（0/5），而从癌症患者获得的细胞系中有3/7是胎儿样的。所有脂肪来源的成纤维细胞（1名非癌症患者和3名癌症患者）也是胎儿样的。我们的结果表明：（i）正常乳腺的FI和FIV成纤维细胞之间存在功能异质性；（ii）在癌旁组织学正常的乳腺组织中存在功能异常（即胎儿样）的FIV成纤维细胞。
