Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
Authors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, TaiwanAuthors' Affiliations: Institute of Microbiology and Immunology, School of Life Science; Department of Biomedical Imaging and Radiological Sciences; School of Medicine, National Yang-Ming University; Department of Education and Research, Taipei City Hospital; Department of Nuclear Medicine; Division of Colorectal Surgery, Department of Surgery; Section of Thoracic Oncology, Chest Department; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital; and VGH Yang-Ming Genome Research Center, Taipei, Taiwan.
Clin Cancer Res. 2014 Jun 1;20(11):2885-97. doi: 10.1158/1078-0432.CCR-13-2162. Epub 2014 Mar 27.
Metastasis is the major cause of death in patients with colorectal cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and serve as a prognostic marker for mortality in clinical stage IV patients. However, most studies are conducted in late-stage cases when distant metastases have already occurred; thus, such results provide limited clinical use. This study focused on whether CTCs can predict the risk of metastasis after treatment of the primary tumor in early-stage patients with CRC.
CTCs were quantified using EpCAM-positive/CD45-negative immunoselection and flow cytometry in patients with CRC. A mouse model was used to investigate the mechanistic roles of CTCs and interleukin (IL)-17A in metastasis.
The number of mesenteric CTCs obtained from stage II patients was higher than that obtained from patients in stages I, III, and IV. In addition, following invasion of orthotopically implanted tumors in our mouse model, we found that CTCs exhibited an increase-then-decrease pattern, accompanied by corresponding changes in serum IL-17A levels and opposing changes in serum granulocyte macrophage colony-stimulating factor (GM-CSF) levels. Ablation of IL-17A and administration of rGM-CSF effectively suppressed the increase in CTCs and prevented metastasis in mice. Moreover, IL-17A promoted cancer cell motility, matrix digestion, and angiogenesis, whereas GM-CSF stimulated the elimination of CTCs by boosting host immunity. Notably, serum levels of IL-17A were also correlated with disease-free survival in patients with CRC.
Our results showed that CTCs and IL-17A could serve as prognostic markers and therapeutic targets for CRC metastasis. Clin Cancer Res; 20(11); 2885-97. ©2014 AACR.
转移是结直肠癌（CRC）患者死亡的主要原因。循环肿瘤细胞（CTC）被认为是转移的原因，并作为临床 IV 期患者死亡的预后标志物。然而，大多数研究都是在已经发生远处转移的晚期病例中进行的；因此，这些结果的临床应用有限。本研究侧重于 CTC 是否可以预测 CRC 早期患者治疗原发性肿瘤后转移的风险。
使用 EpCAM 阳性/CD45 阴性免疫选择和流式细胞术对 CRC 患者进行 CTC 定量。使用小鼠模型研究 CTC 和白细胞介素（IL）-17A 在转移中的机制作用。
从 II 期患者获得的肠系膜 CTC 数量高于 I、III 和 IV 期患者。此外，在我们的小鼠模型中，当肿瘤原位植入后，我们发现 CTC 呈增加-然后减少的模式，同时伴有血清 IL-17A 水平的相应变化和血清粒细胞-巨噬细胞集落刺激因子（GM-CSF）水平的相反变化。IL-17A 的消融和 rGM-CSF 的给药有效地抑制了 CTC 的增加并防止了小鼠的转移。此外，IL-17A 促进癌细胞迁移、基质消化和血管生成，而 GM-CSF 通过增强宿主免疫来刺激 CTC 的消除。值得注意的是，血清中 IL-17A 的水平也与 CRC 患者的无病生存率相关。
我们的结果表明 CTC 和 IL-17A 可以作为 CRC 转移的预后标志物和治疗靶点。临床癌症研究；20(11)；2885-97. ©2014 AACR.
