Colony-stimulating factor-1 and colony-stimulating factor-1 receptor co-expression is associated with disease progression in gastric cancer

  • Authors:
    • Yoshinaga Okugawa
    • Yuji Toiyama
    • Takashi Ichikawa
    • Mikio Kawamura
    • Hiromi Yasuda
    • Hiroyuki Fujikawa
    • Susumu Saigusa
    • Masaki Ohi
    • Toshimitsu Araki
    • Koji Tanaka
    • Yasuhiro Inoue
    • Motoyoshi Tanaka
    • Chikao Miki
    • Masato Kusunoki
  • View Affiliations

  • Published online on: May 16, 2018     https://doi.org/10.3892/ijo.2018.4406
  • Pages: 737-749
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Colony‑stimulating‑factor‑1 (CSF‑1) is a hematopoietic growth factor that exerts its effects through the c‑fms/CSF‑1 receptor (CSF‑1R). The CSF‑1/CSF‑1R axis is thought to be involved in the development of several types of cancer. This study aimed to clarify the clinical and biological significance of the CSF‑1/CSF‑1R axis in gastric cancer (GC). For this purpose, we evaluated CSF‑1 and CSF‑1R expression in GC tissues from 148 patients by RT‑qPCR and immunohistochemistry. The biological roles of the CSF‑1/CSF‑1R axis were investigated by measuring the cell proliferation and migration, and anoikis resistance in a human GC cell line following treatment with recombinant human CSF‑1 and/or CSF‑1R inhibitor. The results revealed that an elevated expression of CSF‑1 or CSF‑1R significantly correlated with disease progression and with a poor overall survival (OS, P=0.037 and 0.016, respectively) and disease‑free survival (DFS, P<0.001 and <0.001, respectively) of patients with GC. Furthermore, a high co‑expression of CSF‑1 and CSF‑1R was an independent prognostic factor for OS (HR, 1.38; 95% CI, 1.02‑1.88; P=0.038) and DFS (HR, 1.79; 95% CI, 1.21‑2.67; P=0.004), and an independent risk factor for lymph node and peritoneal metastasis. Immunohistochemical analysis revealed an intense CSF‑1/CSF‑1R expression in the cytoplasm of cancer cells in primary GC tissues. CSF‑1 or CSF‑1R expression positively correlated with vascular endothelial growth factor A (VEGFA) or Fms related tyrosine kinase 1 (FLT1) expression in GC tissues. Treatment with recombinant human CSF‑1 promoted proliferation, migration and anoikis resistance in a GC cell line. These effects were generally blocked by CSF‑1R inhibition. On the whole, the findings of this study indicate that the CSF‑1/CSF‑1R axis may be a clinically useful prognostic and predictive biomarker for lymph node and peritoneal metastasis and a potential therapeutic target in GC.
View Figures
View References

Related Articles

Journal Cover

August-2018
Volume 53 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Okugawa Y, Toiyama Y, Ichikawa T, Kawamura M, Yasuda H, Fujikawa H, Saigusa S, Ohi M, Araki T, Tanaka K, Tanaka K, et al: Colony-stimulating factor-1 and colony-stimulating factor-1 receptor co-expression is associated with disease progression in gastric cancer. Int J Oncol 53: 737-749, 2018
APA
Okugawa, Y., Toiyama, Y., Ichikawa, T., Kawamura, M., Yasuda, H., Fujikawa, H. ... Kusunoki, M. (2018). Colony-stimulating factor-1 and colony-stimulating factor-1 receptor co-expression is associated with disease progression in gastric cancer. International Journal of Oncology, 53, 737-749. https://doi.org/10.3892/ijo.2018.4406
MLA
Okugawa, Y., Toiyama, Y., Ichikawa, T., Kawamura, M., Yasuda, H., Fujikawa, H., Saigusa, S., Ohi, M., Araki, T., Tanaka, K., Inoue, Y., Tanaka, M., Miki, C., Kusunoki, M."Colony-stimulating factor-1 and colony-stimulating factor-1 receptor co-expression is associated with disease progression in gastric cancer". International Journal of Oncology 53.2 (2018): 737-749.
Chicago
Okugawa, Y., Toiyama, Y., Ichikawa, T., Kawamura, M., Yasuda, H., Fujikawa, H., Saigusa, S., Ohi, M., Araki, T., Tanaka, K., Inoue, Y., Tanaka, M., Miki, C., Kusunoki, M."Colony-stimulating factor-1 and colony-stimulating factor-1 receptor co-expression is associated with disease progression in gastric cancer". International Journal of Oncology 53, no. 2 (2018): 737-749. https://doi.org/10.3892/ijo.2018.4406