Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression
Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression
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DOI：
10.1073/pnas.222537099
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发表时间：
2002-10-29
影响因子：
11.1
通讯作者：
Witte, ON
中科院分区：
文献类型：
--
作者：
Ide, H;Seligson, DB;Witte, ON
集落刺激因子 1 受体 (CSF-1R) 是巨噬细胞发育的主要调节因子，与乳腺癌和卵巢上皮癌相关。对小鼠前列腺发育的免疫组织化学分析表明，在青春期前和雄激素驱动的腺体增殖扩张和分支期间，前列腺芽从泌尿生殖窦突出期间，CSF-1R 上皮表达，但在老年动物中表达下降。小鼠前列腺癌模型显示癌和肿瘤相关巨噬细胞区域有 CSF-1R 表达。几种人前列腺癌细胞系和人前列腺上皮细胞的原代培养物具有较低但可检测到的 CSF-1R 水平。人类前列腺切除样本显示正常腺体或良性前列腺肥大样本中的受体水平较低或无法检测到。染色在前列腺上皮内瘤变或格里森组织学3级或4级癌的区域中最强。在转移性前列腺癌的样品中观察到与磷酸酪氨酸修饰的肽序列特异性的抗体反应的受体的活化形式。免疫组织化学显示巨噬细胞谱系细胞（包括绒毛巨噬细胞和胎盘合体滋养层、肝脏中的 Kupper 细胞以及前列腺癌附近浸润的组织细胞）强烈表达 CSF-1R。这些观察结果将 CSF-1R 表达与正常和肿瘤性前列腺的生长和发育的变化相关联。
Colony-stimulating factor-1 receptor (CSF-1R) is the major regulator of macrophage development and is associated with epithelial cancers of the breast and ovary. Immunohistochemistry analysis of murine prostate development demonstrated epithelial expression of CSF-1R during the protrusion of prostatic buds from the urogenital sinus, during the prepubertal and androgen-driven proliferative expansion and branching of the gland, with a decline in older animals. Models of murine prostate cancer showed CSF-1R expression in areas of carcinoma- and tumor-associated macrophages. Several human prostate cancer cell lines and primary cultures of human prostate epithelial cells had low but detectable levels of CSF-1R. Human prostatectomy samples showed low or undetectable levels of receptor in normal glands or benign prostatic hypertrophy specimens. Staining was strongest in areas of prostatic intraepithelial neoplasia or carcinoma of Gleason histological grade 3 or 4. The activated form of the receptor reactive with antibodies specific for phosphotyrosine modified peptide sequences was observed in samples of metastatic prostate cancer. Immunohistochemistry showed strong expression of CSF-1R by macrophage lineage cells, including villous macrophages and the syncytiotrophoblast layer of placenta, Kupper cells in the liver, and histiocytes infiltrating near prostate cancers. These observations correlate CSF-1R expression with changes in the growth and development of the normal and neoplastic prostate.