Picardo M, Grey A M, McGurk M, Ellis I, Schor S L
Department of Cell & Structural Biology, University of Manchester, England.
Exp Mol Pathol. 1992 Aug;57(1):8-21. doi: 10.1016/0014-4800(92)90044-c.
Fetal skin fibroblasts produce a soluble "migration stimulating factor" (MSF) which is not made by their normal adult counterparts. MSF stimulates the migration of adult skin fibroblasts into 3D collagen gels, thus providing the basis of a convenient bioassay for its presence. We have previously reported that MSF stimulates hyaluronic acid (HA) synthesis by adult skin fibroblasts and that this effect on matrix deposition appears to be responsible for the observed increase in cell motility. In the present study, wound fluid samples were collected from 18 patients undergoing surgery for various nonmalignant conditions and these were then fractionated according to the protocol used to isolate MSF from fetal fibroblast-conditioned medium. Detectable levels of migration stimulating activity were present in 17/18 (94%) of these samples. Paired serum samples obtained both pre- and postoperatively from five patients with positive wound fluid samples were also analyzed for MSF activity; such activity was found in only 1/5 (20%) of the preoperative and 0/5 (0%) of the postoperative serum samples. These data suggest that the MSF present in wound fluid is not derived from a plasma transudate or from platelet degranulation, but may reflect the transient and localized reinitiation of MSF production by adult fibroblasts in response to wounding. Taken together with previous observations regarding the effect of MSF on fibroblast migration and HA synthesis, our data suggest a possible physiological function of MSF in the wound healing response. Previous studies have revealed that MSF is produced by a subpopulation of apparently persistent fetal-like skin fibroblasts obtained from breast cancer patients and is also found in the serum of these individuals. Wound fluid and serum samples were accordingly collected from patients undergoing surgery for various types of malignant conditions or with a previous history of cancer; detectable levels of MSF activity were found in 8/10 (80%) of these wound fluid samples, 2/3 (66.6%) of the preoperative, and 3/3 (100%) of the postoperative paired serum samples. These findings suggest that the presence of detectable serum levels of MSF is not restricted to breast cancer and may be a general feature of malignant disease.
胎儿皮肤成纤维细胞可产生一种可溶性的“迁移刺激因子”（MSF），而其正常的成年对应细胞则不会产生这种因子。MSF可刺激成年皮肤成纤维细胞迁移至三维胶原凝胶中，从而为检测其存在提供了一种便捷的生物测定方法。我们之前曾报道，MSF可刺激成年皮肤成纤维细胞合成透明质酸（HA），且这种对基质沉积的作用似乎是观察到的细胞运动性增加的原因。在本研究中，从18例因各种非恶性疾病接受手术的患者身上采集了伤口液样本，然后按照从胎儿成纤维细胞条件培养基中分离MSF的方案对这些样本进行分级分离。在这些样本中，17/18（94%）的样本检测到了迁移刺激活性。还对5例伤口液样本呈阳性的患者术前和术后采集的配对血清样本进行了MSF活性分析；在术前血清样本中仅1/5（20%）检测到这种活性，术后血清样本中则为0/5（0%）。这些数据表明，伤口液中的MSF并非来自血浆渗出液或血小板脱颗粒，而是可能反映了成年成纤维细胞因受伤而短暂且局部重新启动的MSF产生过程。结合之前关于MSF对成纤维细胞迁移和HA合成影响的观察结果，我们的数据提示了MSF在伤口愈合反应中可能具有的生理功能。之前的研究表明，MSF由从乳腺癌患者身上获取的一群明显持续存在的胎儿样皮肤成纤维细胞产生，并且在这些个体的血清中也能发现。因此，从因各种类型恶性疾病接受手术或有癌症病史的患者身上采集了伤口液和血清样本；在这些伤口液样本中，8/10（80%）检测到了可检测水平的MSF活性，术前配对血清样本中为2/3（66.6%），术后配对血清样本中为3/3（100%）。这些发现表明，血清中可检测到MSF水平并不局限于乳腺癌，可能是恶性疾病的一个普遍特征。
