Kacinski B M
Hunter Radiation Therapy Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA. @Yale.edu
Mol Reprod Dev. 1997 Jan;46(1):71-4. doi: 10.1002/(SICI)1098-2795(199701)46:1<71::AID-MRD11>3.0.CO;2-6.
The expression and function of CSF-1 and its receptor were studied in tumors of the human breast, ovary, and endometrium. CSF-1 and its receptor, initially implicated as essential to normal monocyte development and trophoblastic implantation, have been more recently shown to be expressed by carcinomas of the breast and other epithelia of the female reproductive tract where activation of the receptor by ligand produced either by the tumor cells or by stromal elements stimulates tumor cell invasion by a urokinase-dependent mechanism. Breast carcinomas express wild-type CSF-1 receptors (CSF-1R) at levels comparable to those observed in trophoblast and monocytes. Ovarian and endometrial carcinomas express significantly lower levels of wild-type, functional CSF-1Rs, while ovarian carcinomas also express unusual transcripts that diverge from the wild-type CSF-1R transcript in their 5' extracellular domain sequences. Tumor cell expression of CSF-1R is under the control of several steroid hormones (glucocorticoids and progestins) and the binding of several bHLH transcription factors, while tumor cell expression of CSF-1 appears to be regulated by other hormones, some of which are involved in normal lactogenic differentiation. In addition, tumor cells often produce CSF-1 at such high levels that the cytokine spills into the extracellular fluid and circulation. Measurements of circulating levels of CSF-1 have proved useful in patients with ovarian, endometrial, and breast carcinoma both for disease detection and monitoring of response to therapy. CSF-1 and its receptor appear to be an important receptor/ligand pair in the biology of breast cancers and tumors of the female reproductive tract where they may regulate functions similar to those they control during macrophage activation and placental implantation.
在人乳腺癌、卵巢癌和子宫内膜癌中研究了集落刺激因子-1（CSF-1）及其受体的表达和功能。CSF-1及其受体最初被认为对正常单核细胞发育和滋养层植入至关重要，最近研究表明，它们在乳腺癌及女性生殖道其他上皮癌中表达，肿瘤细胞或基质成分产生的配体激活受体后，通过尿激酶依赖性机制刺激肿瘤细胞侵袭。乳腺癌表达的野生型CSF-1受体（CSF-1R）水平与滋养层细胞和单核细胞中的水平相当。卵巢癌和子宫内膜癌表达的野生型功能性CSF-1R水平显著较低，而卵巢癌还表达异常转录本，其5'细胞外结构域序列与野生型CSF-1R转录本不同。CSF-1R的肿瘤细胞表达受几种类固醇激素（糖皮质激素和孕激素）以及几种bHLH转录因子结合的控制，而CSF-1的肿瘤细胞表达似乎受其他激素调节，其中一些激素参与正常泌乳分化。此外，肿瘤细胞通常会产生高水平的CSF-1，以至于细胞因子会溢出到细胞外液和循环中。测量CSF-1的循环水平已被证明对卵巢癌、子宫内膜癌和乳腺癌患者在疾病检测和治疗反应监测方面都很有用。CSF-1及其受体似乎是乳腺癌和女性生殖道肿瘤生物学中的重要受体/配体对，它们在其中可能调节与巨噬细胞激活和胎盘植入过程中所控制的功能类似的功能。
