Smith H O, Anderson P S, Kuo D Y, Goldberg G L, DeVictoria C L, Boocock C A, Jones J G, Runowicz C D, Stanley E R, Pollard J W
Department of Obstetrics and Gynecology, Department of Developmental and Molecular Biology, and Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461, USA.
Clin Cancer Res. 1995 Mar;1(3):313-25.
Colony-stimulating factor 1 (CSF-1) is a homodimeric growth factor that humorally regulates the growth and differentiation of mononuclear phagocytes, and locally regulates maternal-fetal interactions during pregnancy. It exerts these actions through a transmembrane tyrosine kinase receptor, colony-stimulating factor 1 receptor (CSF-1R), the product of the c-fms proto-oncogene. Recent studies have demonstrated overexpression of CSF-1 and its receptor in breast, ovarian, and endometrial adenocarcinomas. To further investigate the possible role of CSF-1 and its receptor in the pathogenesis of endometrial adenocarcinoma, a prospective study was undertaken to study CSF-1 expression in benign and neoplastic endometrial epithelium and to compare serum CSF-1 levels in endometrial adenocarcinoma patients with healthy perimenopausal women. The mean serum levels of CSF-1 in 71 patients with endometrial cancer (4.9 +/- 1.8 microgram/liter) were significantly elevated compared with levels found in the 32 controls (3.5 +/- 1.1 microgram/liter). Within the endometrial adenocarcinoma group, circulating CSF-1 levels were significantly elevated in patients with large tumor volume, high grade, myometrial invasion, residual disease, and circulating CA-125 levels. High serum levels of serum CSF-1 were associated with elevated serum CA19-9 and CA-125 levels. Immunohistochemistry results revealed in tumor epithelium intense staining for CSF-1R (27 of 54 cases, 50%) and elevated staining for CSF-1 (41 of 54 cases, 75.9%), with intense staining of CSF-1 in 16 of 54 cases (29.6%). Staining was significantly greater in intensity and number of cells involved in malignant compared with benign epithelium for CSF-1R and CSF-1 (P = 0.05 and <0.0001, respectively). A positive correlation between amount and intensity of CSF-1 and CSF-1R staining in endometrial adenocarcinoma tissue was also demonstrated (P = 0.007). CSF-1 and CSF-1R mRNA was also detected in the tumor samples, confirming the expression of the protein in these tissues. Reverse transcription-PCR demonstrated the presence of mRNA for both the transmembrane and secreted forms of CSF-1 in all tumors analyzed. These results therefore support the hypotheses that CSF-1 and CSF-1R are overexpressed in endometrial adenocarcinoma, that levels of expression significantly correlate with clinicopathological risk factors for poor outcome, and that CSF-1 in association with its receptor via autocrine, juxtacrine, and/or paracrine interactions has a causal role in endometrial adenocarcinoma development and proliferation.
集落刺激因子1（CSF-1）是一种同二聚体生长因子，可通过体液调节单核吞噬细胞的生长和分化，并在妊娠期间局部调节母胎相互作用。它通过跨膜酪氨酸激酶受体——集落刺激因子1受体（CSF-1R，即原癌基因c-fms的产物）发挥这些作用。最近的研究表明，CSF-1及其受体在乳腺癌、卵巢癌和子宫内膜腺癌中过表达。为了进一步研究CSF-1及其受体在子宫内膜腺癌发病机制中的可能作用，进行了一项前瞻性研究，以研究CSF-1在良性和肿瘤性子宫内膜上皮中的表达，并比较子宫内膜腺癌患者与健康围绝经期妇女的血清CSF-1水平。71例子宫内膜癌患者的CSF-1平均血清水平（4.9±1.8微克/升）与32例对照组患者（3.5±1.1微克/升）相比显著升高。在子宫内膜腺癌组中，肿瘤体积大、分级高、肌层浸润、有残留病灶以及循环CA-125水平高的患者，其循环CSF-1水平显著升高。血清CSF-1水平高与血清CA19-9和CA-125水平升高相关。免疫组织化学结果显示，肿瘤上皮中CSF-1R呈强染色（54例中的27例，50%），CSF-1染色增强（54例中的41例，75.9%），其中16例（29.6%）CSF-1呈强染色。与良性上皮相比，恶性上皮中CSF-1R和CSF-1的染色强度和涉及的细胞数量显著更高（分别为P = 0.05和<0.0001）。子宫内膜腺癌组织中CSF-1和CSF-1R染色的量和强度之间也存在正相关（P = 0.007）。在肿瘤样本中也检测到了CSF-1和CSF-1R mRNA，证实了这些组织中蛋白质的表达。逆转录聚合酶链反应表明，在所有分析的肿瘤中均存在跨膜和分泌形式的CSF-1的mRNA。因此，这些结果支持以下假设：CSF-1和CSF-1R在子宫内膜腺癌中过表达，表达水平与预后不良的临床病理危险因素显著相关，并且CSF-1与其受体通过自分泌、旁分泌和/或近分泌相互作用在子宫内膜腺癌的发生和增殖中起因果作用。
