Open Access

SDF1α/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment

  • Authors:
    • Masakazu Yashiro
    • Haruhito Kinoshita
    • Gen Tsujio
    • Tatsunari Fukuoka
    • Yurie Yamamoto
    • Tomohiro Sera
    • Atsushi Sugimoto
    • Sadaaki Nishimura
    • Shuhei Kushiyama
    • Shingo Togano
    • Kenji Kuroda
    • Takahiro Toyokawa
    • Masaichi Ohira
  • View Affiliations

  • Published online on: November 12, 2020     https://doi.org/10.3892/ol.2020.12299
  • Article Number: 38
  • Copyright: © Yashiro et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Stromal cell‑derived factor 1α (SDF1α) and its receptor C‑X‑C chemokine receptor type 4 (CXCR4) have been reported to form an important chemokine signaling pathway. Our previous study reported that SDF1α from tumor stromal cells may stimulate the proliferation of gastric cancer (GC) cells through the CXCR4 axis in a hypoxic microenvironment. However, a limited number of studies have addressed the clinicopathological significance of the expression of SDF1α and CXCR4 in GC, particularly at hypoxic regions. Immunohistochemistry was used to investigate the expression levels of SDF1α, CXCR4 and the hypoxic marker carbonic anhydrase 9 (CA9) in 185 patients with stage II and III GC. The results demonstrated that CA9 was expressed on cancer and stromal cells in hypoxic lesions, CXCR4 was mainly expressed in cancer cells, and SDFα was mainly expressed in stromal cells. CXCR4 expression in cancer cells and SDFα expression in stromal cells were associated with the hypoxic regions with CA9 expression. The CA9 and CXCR4 expression in the cancer cells, and the SDF1α expression in the stromal cells (CA9/CXCR4/SDF1α) was significantly associated with macroscopic type 4 tumor (P=0.012) and the pattern of tumor infiltration into the surrounding tissue (P<0.001). The prognosis of the all CA9/CXCR4/SDF1α‑positive patients was significantly poorer compared with that of patients with CA9‑, CXCR4‑ or SDF1α‑negative GC at Stage III (P=0.041). These results indicated that hypoxia may upregulate SDFα production in stromal cells and CXCR4 expression in cancer cells. The SDF1α/CXCR4 axis may serve an important role in the progression of GC.
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January-2021
Volume 21 Issue 1

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Spandidos Publications style
Yashiro M, Kinoshita H, Tsujio G, Fukuoka T, Yamamoto Y, Sera T, Sugimoto A, Nishimura S, Kushiyama S, Togano S, Togano S, et al: SDF1&alpha;/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment. Oncol Lett 21: 38, 2021.
APA
Yashiro, M., Kinoshita, H., Tsujio, G., Fukuoka, T., Yamamoto, Y., Sera, T. ... Ohira, M. (2021). SDF1&alpha;/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment. Oncology Letters, 21, 38. https://doi.org/10.3892/ol.2020.12299
MLA
Yashiro, M., Kinoshita, H., Tsujio, G., Fukuoka, T., Yamamoto, Y., Sera, T., Sugimoto, A., Nishimura, S., Kushiyama, S., Togano, S., Kuroda, K., Toyokawa, T., Ohira, M."SDF1&alpha;/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment". Oncology Letters 21.1 (2021): 38.
Chicago
Yashiro, M., Kinoshita, H., Tsujio, G., Fukuoka, T., Yamamoto, Y., Sera, T., Sugimoto, A., Nishimura, S., Kushiyama, S., Togano, S., Kuroda, K., Toyokawa, T., Ohira, M."SDF1&alpha;/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment". Oncology Letters 21, no. 1 (2021): 38. https://doi.org/10.3892/ol.2020.12299